Tack-Joong Kim

Publications of Tack-Joong Kim

• Anti-inflammatory and anti-allergic effects of Agrimonia pilosa Ledeb extract on murine cell lines and OVA-induced airway inflammation.

  Authors: Jae-Jin Kim, Jun Jiang, Do-Wan Shim, Sang-Chul Kwon, Tack-Joong Kim, Sang-Kyu Ye, Myong-Ki Kim, Yong-Kook Shin, Sushruta Koppula, Tae-Bong Kang, Dong-Kug Choi, Kwang-Ho Lee

  Journal of ethnopharmacology. 03/2012; 140(2):213-21.

  ETHNOPHARMACOLOGICAL EVIDENCE: Agrimonia pilosa Ledeb (Rosaceae, AP) has long been used as a traditional medicine in Korea and other Asian countries to treat various diseases. In the present study,ETHNOPHARMACOLOGICAL EVIDENCE: Agrimonia pilosa Ledeb (Rosaceae, AP) has long been used as a traditional medicine in Korea and other Asian countries to treat various diseases. In the present study, the anti-inflammatory and anti-allergic effects of AP extract in in vitro cell lines and in vivo mouse model of inflammation and the molecular mechanisms involved were reported. Using Raw 264.7 murine macrophages the effects of methanol extract of AP in lipopolysaccharide (LPS)-induced production of inflammatory mediators were measured. Further IgE-DNP-induced interleukin (IL)-4 production and degranulation in RBL-2H3 rat basophilic cell lines was also estimated. To investigate the anti-asthmatic effect of AP in vivo, airway inflammation in ovalbumin (OVA)-induced mouse model was used. AP attenuated the production of inflammatory mediators such as NO, PGE(2) and pro-inflammatory cytokines in LPS-induced Raw 264.7 cells. Further, AP inhibited IL-4 production and degranulation in IgE-DNP-induced RBL-2H3 cells. Furthermore, AP attenuated the infiltration of immune cells into lung, cytokines production in broncho-alveolar lavage fluid (BALF) and airway-hyperresponsiveness (AHR) on OVA-induced mouse model of inflammation. Our results showed that AP attenuated the activation of macrophages, basophils, and inhibited the OVA-induced airway inflammation. The molecular mechanisms leading to AP's potent anti-inflammatory and anti-allergic effects might be through regulation of TRIF-dependent and Syk-PLCγ/AKT signaling pathways, suggesting that AP may provide a valuable therapeutic strategy in treating various inflammatory diseases including asthma.

• Diethylstilbestrol induces arrest of rat vascular smooth muscle cell cycle progression through downregulation of cyclin D1 and cyclin E.

  Authors: Min-Cheol Song, Junsoo Park, Tack-Joong Kim

  Molecular and cellular biochemistry. 09/2011; 360(1-2):103-9.

  Cardiovascular disease is associated with a multitude of pathophysiologic conditions, including vascular smooth muscle cell (VSMC) proliferation in response to vessel injury. Diethylstilbestrol (DES)Cardiovascular disease is associated with a multitude of pathophysiologic conditions, including vascular smooth muscle cell (VSMC) proliferation in response to vessel injury. Diethylstilbestrol (DES) was previously prescribed for at-risk pregnancies to prevent abortion, miscarriage, and premature labor. Our aim in this study was to elucidate the effects and molecular mechanism of DES on proliferation and cell cycle progression of platelet-derived growth factor (PDGF)-BB-stimulated rat aortic VSMCs. Treating the cells with DES (1-7 μM) dramatically inhibited cell proliferation in a dose-dependent manner without any cytotoxic effects. In addition, DES blocked cell cycle progression from PDGF-BB-stimulated cells, which we found was related to down-regulation of the cell cycle regulatory factors, cyclin D1, and cyclin E. Our data demonstrate that DES inhibits rat aortic VSMC proliferation and cell cycle progression through regulation of cell cycle-related proteins. Therefore, our observations may explain, in part, the mechanistic basis underlying the therapeutic effects of DES in cardiovascular disease.

• Temporal expression profiles of ceramide and ceramide-related genes in wild-type and mPer1/mPer2 double knockout mice.

  Authors: Yeong-Su Jang, Yeo-Jin Kang, Tack-Joong Kim, Kiho Bae

  Molecular biology reports. 07/2011; 39(4):4215-21.

  Most living organisms exhibit circadian rhythms in physiology and behavior. These oscillations are generated by an endogenous circadian clock and control many biological processes. Ceramide hasMost living organisms exhibit circadian rhythms in physiology and behavior. These oscillations are generated by an endogenous circadian clock and control many biological processes. Ceramide has attracted attention as a signal mediator in diverse cell processes including cell death and differentiation. The relationships between ceramide expression levels and the circadian clock have not previously been investigated. To determine if there are circadian variations in the content of ceramide, we measured ceramide concentrations in the livers of wild-type (WT) and mPer1/mPer2 double knockout (DKO) mice. The ceramide concentration in WT mice was dramatically increased at Zeitgeber Time 9 (ZT9; 9 h after lights-on time) and ZT21 but no rhythmicity in ceramide expression was seen in DKO mice. Because ceramide can be generated by the hydrolysis of sphingomyelin via sphingomyelinase (SMase), or by ceramide synthase (CerS)-mediated synthesis, we assayed the expression patterns of ceramide-related genes using real-time PCR. CerS2 expression levels showed a biphasic pattern of expression in WT mice but no rhythmicity in DKO mice. While the neutral SMase (nSMase) and acidic SMase (aSMase) mRNA in WT mice were expressed in a circadian manner, the correlation between the expression levels of these SMases with times of day was weak in DKO mice. Collectively, our findings suggest that both SMases and CerS2 mRNA expression are regulated by the presence of mPer1/mPer2 circadian clock genes in vivo, and imply that ceramide may play a vital role in circadian rhythms and physiology.

• Major constituents and antimicrobial activity of Korean herb Acorus calamus.

  Authors: Wan-Jae Kim, Keum-Hee Hwang, Dong-Geun Park, Tack-Joong Kim, Dong-Woo Kim, Dong-Kug Choi, Won-Kook Moon, Kwang-Ho Lee

  Natural product research. 06/2011; 25(13):1278-81.

  The constituents and antimicrobial activity of the essential oil from Acorus calamus were analysed. Methyl isoeugenol and cyclohexanone were identified as the major constituents of the essential oil.The constituents and antimicrobial activity of the essential oil from Acorus calamus were analysed. Methyl isoeugenol and cyclohexanone were identified as the major constituents of the essential oil. The essential oil was tested for antimicrobial activity against bacteria and yeast, and has shown strong antibiotic activities against most of the tested microbes, except Escherichia coli. The hexane extract has shown a similar pattern of antimicrobial activity as the essential oil. Methyl isoeugenol, the most abundant constituent in the essential oil, has also shown similar antimicrobial activity, except against Bacillus subtilis. The essential oil as well as the hexane extract and methyl isoeugenol have shown antimicrobial activity against Propionibacterium acne, which is known to be involved in acne vulgaris.

• MyD88-dependent Toll-like receptor signaling is required for murine macrophages response to IS2.

  Authors: Hua Li, Wan-Jae Kim, Jun Jiang, Seung-Hwan Lee, Hyung-Sun Youn, Eun-Yi Moon, Tack-Joong Kim, Sang-Kyu Ye, Ji-Hwan Ryu, Tae-Bong Kang, Sushruta Koppula, Pyo-Jam Park, Dong-Kug Choi, Kwang-Ho Lee

  International immunopharmacology. 05/2011; 11(10):1578-83.

  IS2, a soluble β-glucan isolated from the cell wall of mutated Saccharomyces cerevisiae (S. cerevisiae) enhances the immune response compared to the wild type (WT) β-glucan. In the presentIS2, a soluble β-glucan isolated from the cell wall of mutated Saccharomyces cerevisiae (S. cerevisiae) enhances the immune response compared to the wild type (WT) β-glucan. In the present investigation we report that Toll-like receptor (TLR)/MyD88 signaling pathway was responsible in IS2 β-glucan-mediated cellular response in RAW264.7 murine macrophages. Data revealed that IS2 β-glucan significantly up-regulated the TLR2/TLR4 expression. Moreover, TLR2/TLR4 responds to IS2 resulting in murine macrophage activation. In addition, the IS2 signal led to cytokine secretions of IL-6 and TNF-α. In the case of thioglycolate-elicited peritoneal macrophages from MyD88-deficient mice, the decrease in cytokines was observed. Further the mitogen-activated protein kinases (MAPKs) phosphorylation was evident and degradation of IκB-α was increased after stimulation with IS2 β-glucan. Further examination with MyD88-deficient mice revealed that the MyD88 pathway might play an important role for IS2 β-glucan-mediated activation of macrophages.

• Ceramide 1-phosphate induces neointimal formation via cell proliferation and cell cycle progression upstream of ERK1/2 in vascular smooth muscle cells.

  Authors: Tack-Joong Kim, Yeo-Jin Kang, Yong Lim, Hyoung-Woo Lee, Kiho Bae, Youn-Sun Lee, Jae-Myung Yoo, Hwan-Soo Yoo, Yeo-Pyo Yun

  Experimental cell research. 05/2011; 317(14):2041-51.

  Ceramide 1-phosphate (C1P) is a novel bioactive sphingolipid formed by ceramide kinase (CERK)-catalyzed phosphorylation of ceramide. It has been implicated in the regulation of such vitalCeramide 1-phosphate (C1P) is a novel bioactive sphingolipid formed by ceramide kinase (CERK)-catalyzed phosphorylation of ceramide. It has been implicated in the regulation of such vital pathophysiological functions as phagocytosis and inflammation, but there have been no reports ascribing a biological function to CERK in vascular disorders. Here the potential role of CERK/C1P in neointimal formation was investigated using rat aortic vascular smooth muscle cells (VSMCs) in primary culture and a rat carotid injury model. Exogenous C8-C1P stimulated cell proliferation, DNA synthesis, and cell cycle progression of rat aortic VSMCs in primary culture. In addition, wild-type CERK-transfected rat aortic VSMCs induced a marked increase in rat aortic VSMC proliferation and [(3)H]-thymidine incorporation when compared to empty vector transfectant. C8-C1P markedly activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) within 5min, and the activation could be prevented by U0126, a MEK inhibitor. Also, K1, a CERK inhibitor, decreased the ERK1/2 phosphorylation and cell proliferation on platelet-derived growth factor (PDGF)-stimulated rat aortic VSMCs. CERK expression and C1P levels were found to be potently increased during neointimal formation using a rat carotid injury model. However, ceramide levels decreased during the neointimal formation process. These findings suggest that C1P can induce neointimal formation via cell proliferation through the regulation of the ERK1/2 protein in rat aortic VSMCs and that CERK/C1P may regulate VSMC proliferation as an important pathogenic marker in the development of cardiovascular disorders.

• Alpinumisoflavone induces apoptosis and suppresses extracellular signal-regulated kinases/mitogen activated protein kinase and nuclear factor-κB pathways in lung tumor cells.

  Authors: Sim Namkoong, Tack-Joong Kim, Ik-Soon Jang, Keon-Wook Kang, Won-Keun Oh, Junsoo Park

  Biological & pharmaceutical bulletin. 01/2011; 34(2):203-8.

  The extracellular signal-regulated kinases/mitogen activated protein kinase (ERK/MAPK) and nuclear factor-κB (NF-κB) pathways are critical for cell survival and proliferation. AlpinumisoflavoneThe extracellular signal-regulated kinases/mitogen activated protein kinase (ERK/MAPK) and nuclear factor-κB (NF-κB) pathways are critical for cell survival and proliferation. Alpinumisoflavone (AIF), isolated from the African medicinal plant Erythrina lysistemon, is a member of the isoflavone group. In this report, we demonstrated that AIF treatment induces cell death of human lung tumor cells. Incubation of lung tumor cells with AIF increased the sub-G1 population and caspase 3/7 activity, suggesting that the cell death is caused by apoptosis. To identify the signaling pathway involved in the tumor cell death, we examined the modulation of transcriptional activity using various reporter constructs and found that AIF significantly deregulated both the ERK/MAPK and NF-κB pathways. Western blot analysis with antibodies to MAP/ERK kinase (MEK) and ERK showed that AIF dephosphorylates both MEK and ERK. Alpinumisoflavone also repressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells by inhibiting NF-κB-dependent transcription. Therefore, the cell death induced by AIF may be via repressing both the ERK/MAPK and NF-κB pathways.

• Sauchinone attenuates oxidative stress-induced skeletal muscle myoblast damage through the down-regulation of ceramide.

  Authors: Min-Ho Jung, Min-Cheol Song, Kiho Bae, Han Sung Kim, Seung Hyun Kim, Sang Hyun Sung, Sang Kyu Ye, Kwang Ho Lee, Yeo-Pyo Yun, Tack-Joong Kim

  Biological & pharmaceutical bulletin. 01/2011; 34(4):575-9.

  We investigated the effects of sauchinone, isolated from the root of Saururus chinensis, on muscle disorders and the underlying mechanism of oxidative stress-induced C(2)C(12) skeletal muscleWe investigated the effects of sauchinone, isolated from the root of Saururus chinensis, on muscle disorders and the underlying mechanism of oxidative stress-induced C(2)C(12) skeletal muscle myoblast damage. To assess the protective effects of sauchinone on oxidative stress-induced C(2)C(12) skeletal muscle myoblasts, we measured the viability of the cells, showing that sauchinone pre-treatment significantly reduced the decreased cell viability after H(2)O(2) treatment. We also investigated the mechanism of this protective effect of sauchinone. In Western blot analysis, the heat shock protein (HSP)-70 level increased significantly in the sauchinone-pretreated myoblasts. We used high performance liquid chromatography (HPLC) to examine the level of endogenous ceramide after pre-treatment with sauchinone followed by exposure to H(2)O(2). While hydrogen peroxide increased the ceramide content to approximately 166.60±38.93% of the control level, pre-treatment with sauchinone inhibited this increase, maintaining the ceramide content at the control level. We demonstrated that sauchinone regulates intracellular HSP70 expression as well as ceramide levels to protect against oxidative stress-induced C(2)C(12) muscle myoblast damage. We suggest the potential benefits of herbal medicines in the treatment of oxidative stress-related muscle disorders.

• Gold nanoparticles attenuate LPS-induced NO production through the inhibition of NF-kappaB and IFN-beta/STAT1 pathways in RAW264.7 cells.

  Authors: Ji Su Ma, Wan Jae Kim, Jae Jin Kim, Tack Joong Kim, Sang Kyu Ye, Min Dong Song, Hyun Kang, Dong Woo Kim, Won Kook Moon, Kwang Ho Lee

  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society. 11/2010; 23(3):214-9.

  Macrophage-derived nitric oxide (NO) plays an important role in protection against microbial infection in immune responses. Overproduction of NO by inducible nitric synthase (iNOS) is known to beMacrophage-derived nitric oxide (NO) plays an important role in protection against microbial infection in immune responses. Overproduction of NO by inducible nitric synthase (iNOS) is known to be closely correlated with the pathology of a variety of diseases and inflammations. In this study, we investigated the inhibitory effect of polyethylene glycol coated gold nanoparticles (GNP) on NO production and its molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. It was found that GNP inhibited LPS-induced NO production and iNOS expression in RAW264.7 cells. Furthermore, GNP suppressed LPS-induced activation of NF-kappaB through the inhibition of Akt activity. GNP also inhibited LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) via down-regulation of interferon-beta (IFN-beta) expression. Our results suggest that GNP inhibits NO production and iNOS expression through blocking the activation of NF-kappaB and STAT1 in LPS-stimulated RAW264.7 cells.

• Inhibitory effect of fenofibrate on neointima hyperplasia via G(0)/G(1) arrest of cell proliferation.

  Authors: Jung-Jin Lee, Ji-Yeon Yu, Wei-Yun Zhang, Tack-Joong Kim, Yong Lim, Jin-Sook Kwon, Dong-Woon Kim, Chang-Seon Myung, Yeo-Pyo Yun

  European journal of pharmacology. 10/2010; 650(1):342-9.

  We have previously reported that fenofibrate displayed a potent antithrombotic effect by the inhibition of platelet aggregation. The present study was designed to investigate the effects ofWe have previously reported that fenofibrate displayed a potent antithrombotic effect by the inhibition of platelet aggregation. The present study was designed to investigate the effects of fenofibrate on the neointimal hyperplasia and its possible molecular mechanism. Neointimal hyperplasia was measured in balloon-inflated-induced vascular injury model of male Sprague-Dawley rats and cell proliferation was measured in primary cultured rat aortic vascular smooth muscle cells (VSMCs). Fenofibrate-treated group showed a significant reduction in neointimal formation (0.07±0.04mm(2)) from the control (0.13±0.04mm(2)). Fenofibrate significantly inhibited platelet-derived growth factor (PDGF)-BB-induced cell counting and [(3)H]-thymidine incorporation into DNA. Fenofibrate suppressed the PDGF-BB-inducible progression through G(0)/G(1) to S phase of cell cycle. Moreover, fenofibrate inhibited not only phosphorylation of retinoblastoma (Rb) protein and expression of cyclin D/E, CDK 2/4 and proliferating cell nuclear antigen (PCNA) proteins but also mitogen-activated protein kinase (MAPK) signaling pathways such as ERK 1/2, p38 and JNK phosphorylation. In conclusion, the present study demonstrates that fenofibrate significantly inhibits neointimal formation via G(0)/G(1) arrest of PDGF-BB-induced cell proliferation in association with the inhibition of MAPK, which resulted in the downregulation of expressions of cyclin D/E, CDK 2/4 and PCNA proteins, suggesting that fenofibrate may be useful for individuals with a high risk of thrombotic or cardiovascular diseases.

• The protective effects of paclitaxel on platelet aggregation through the inhibition of thromboxane A2 synthase.

  Authors: Jung-Jin Lee, Ji-Yeon Yu, Joo-Hyung Lee, Wei Yun Zhang, Tack-Joong Kim, Chang-Seon Myung, Yeo-Pyo Yun

  Archives of pharmacal research. 03/2010; 33(3):387-94.

  Paclitaxel is an anticancer drug used in the treatment of ovarian, breast, head and neck, lung, and prostate cancer. We investigated the antiplatelet activity of paclitaxel in vitro as well as aPaclitaxel is an anticancer drug used in the treatment of ovarian, breast, head and neck, lung, and prostate cancer. We investigated the antiplatelet activity of paclitaxel in vitro as well as a possible antiplatelet mechanism. Paclitaxel inhibited washed rabbit platelet aggregation induced by collagen in a concentration dependent manner, with an IC(50) of 59.7 +/- 3.5. However, it had little effect on platelet aggregation mediated by arachidonic acid, U46619, a thromboxane (TX) A(2) mimic, or thrombin, suggesting that paclitaxel may strongly inhibit collagen mediated signal transduction. In accordance with these findings, paclitaxel blocked collagen induced cytosolic calcium mobilization, arachidonic acid liberation, and serotonin secretion. In addition, it inhibited arachidonic acid mediated platelet aggregation by about 37% by interfering with TXA(2) synthase as measured by the formation of arachidonic acid mediated TXA(2) and prostaglandin D(2), as well as cyclooxygenase-1 and TXA(2) synthase activity assays. Taken together, these results point to a cellular mechanism for the antiplatelet activity of paclitaxel through the inhibition of TXA(2) synthase and cytosolic calcium mobilization. This may contribute to the beneficial effects of paclitaxel on the cardiovascular system.

• CADPE suppresses cyclin D1 expression in hepatocellular carcinoma by blocking IL-6-induced STAT3 activation.

  Authors: Cheolhee Won, Chang Seok Lee, Jin-Ku Lee, Tack-Joong Kim, Kwang-Ho Lee, Young Mok Yang, Yong-Nyun Kim, Sang-Kyu Ye, Myung-Hee Chung

  Anticancer research. 02/2010; 30(2):481-8.

  The initiation and growth of hepatocellular carcinoma (HCC) are closely linked to chronic inflammation. Not only is cyclin D1 overexpressed, but it is also related to aggressive progression in HCC.The initiation and growth of hepatocellular carcinoma (HCC) are closely linked to chronic inflammation. Not only is cyclin D1 overexpressed, but it is also related to aggressive progression in HCC. However, the mechanism of expression cyclin D1, a cell-cycle regulator of paramount importance, in the tumor microenvironment remains unknown. Here, we investigated the mechanism of cyclin D1 expression induced by interleukin-6 (IL-6) and whether 3-[3,4-dihydroxy-phenyl]-acrylic acid 2-[3,4-dihydroxy-phenyl]-ethyl ester (CADPE), a derivate of caffeic acid, suppresses cyclin D1 expression. CADPE significantly inhibited IL-6-induced signal transducer and activator of transcription 3 (STAT3) activity in the Huh7 HCC cell line and attenuated IL-6-induced cyclin D1 transcription. Moreover, overexpression of constitutively active STAT3 increased cyclin D1 transcriptional activity and protein expression, whereas overexpression of a dominant-negative STAT3 deletion mutant (STAT3 (1-588)) reduced cyclin D1 transcriptional activity. In addition, CADPE effectively deacetylated histone 4 and prevented STAT3 recruitment to the cyclin D1 promoter, consistent with a role for the CADPE target, STAT3, in the regulation of cyclin D1 transcription. Collectively, these results indicate that CADPE suppresses cyclin D1 expression in HCC cells by blocking both IL-6-mediated STAT3 activation and recruitment of STAT3 to the cyclin D1 promoter.

• Inhibitory effects of BST406, a newly synthesized benzylideneacetophenone derivative, on abnormal vascular smooth muscle cell proliferation.

  Authors: Tack-Joong Kim, Hyeong-Jun Han, Yong-Jae Kim, Jae-Chul Jung, Ji-Yeon Yu, Jung-Jin Lee, Yeo-Pyo Yun

  Biological & pharmaceutical bulletin. 01/2010; 33(5):900-4.

  Benzylideneacetophenone analogues are known to have several significant biological activities, including antiinflammatory, antitumor, antibacterial, antiviral, and gastric-protective activities.Benzylideneacetophenone analogues are known to have several significant biological activities, including antiinflammatory, antitumor, antibacterial, antiviral, and gastric-protective activities. However, the antiproliferative effects of benzylideneacetophenone analogues on vascular smooth muscle cells (VSMCs) are unknown. The aim of this study was to elucidate the antiproliferative effects and molecular mechanism of BST406, a newly synthesized benzylideneacetophenone derivative, on platelet-derived growth factor (PDGF)-BB-stimulated rat aortic VSMCs. BST406 inhibited [(3)H]-thymidine incorporation into DNA in VSMCs following treatment with PDGFBB 25 ng/ml. PDGF-BB-stimulated DNA synthesis was significantly reduced. Moreover, pretreatment with BST406 (0-10microM) suppressed the proliferation of PDGF-BB-stimulated cells in a concentration-dependent manner. We also investigated the mechanism of the antiproliferative effects of BST406 in PDGF-BB-stimulated VSMCs. In Western blot analysis, PDGF-BB-stimulated (25 ng/ml) phospholipase-C (PLC)gamma1 and Akt phosphorylation was inhibited by BST406 (0-10microM). However, BST406 did not inhibit the PDGF-receptor beta-chain (PDGF-Rbeta) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation induced by PDGF-BB. To confirm that the inhibitory effects of BST406 are mediated through the inhibition of PLCgamma1 or Akt, the effects of inhibitors on cell viability were examined. U73122 completely inhibited PDGF-BB-induced proliferation of VSMCs. However, LY294002 10microM had no significant effects on PDGF-BB-induced proliferation. These findings suggest that the inhibitory effects of BST406 on the proliferation of PDGF-BB-stimulated VSMCs are mediated by suppression of the PLCgamma1 signaling pathways. Our observations may explain, in part, the mechanistic basis for the prevention of cardiovascular disease (such as atherosclerosis and restenosis after coronary angioplasty) by BST406.

• Idesolide, an isolate of Idesia polycarpa, inhibits apoptosis through induction of intracellular heat shock protein 70 in C2C12 muscle cells.

  Authors: Min-Ho Jung, Jung-Min Yoo, Yeo-Jin Kang, Hyoung Woo Lee, Seung Hyun Kim, Sang Hyun Sung, Yong-Jin Lee, Inho Choi, Tack-Joong Kim

  Biological & pharmaceutical bulletin. 01/2010; 33(6):1063-6.

  Muscle disorders, such as muscular dystrophy, are associated with an increase in oxidative stress. Proposed treatments for muscular dystrophy, some in clinical trials, include gene therapy and muscleMuscle disorders, such as muscular dystrophy, are associated with an increase in oxidative stress. Proposed treatments for muscular dystrophy, some in clinical trials, include gene therapy and muscle cell transplantation. In this study, we investigated the effects of idesolide, isolated from the fruits of Idesia polycarpa, on changes that occur in muscle disuse atrophy. We noted protective effects on oxidative stress response and HSP70 regulation. Pre-treatment with idesolide for 24 h maintained cell viability and decreased apoptosis in H(2)O(2)-treated C(2)C(12) muscle cells. The idesolide pretreatment also increased intracellular HSP70 protein. Our results suggest that idesolide inhibits cell death through induction of HSP70 in C(2)C(12) muscle cells. This work is the first to report that idesolide can regulate the decrease in HSP70 that occurs during skeletal muscle atrophy.

• JY0691, a newly synthesized obovatol derivative, inhibits cell cycle progression of rat aortic smooth muscle cells through up-regulation of p21(cip1).

  Authors: Ji-Yeon Yu, Jung-Jin Lee, Jae-Kyung Jung, Tack-Joong Kim, Hwan-Soo Yoo, Yeo-Pyo Yun, Jeong-Chae Lee

  European journal of pharmacology. 10/2009;

  Obovatol is known to have various biological activities such as muscle relaxation, anti-gastric ulcer, anti-inflammatory, anti-allergic, and anti-bacterial activities. We examined the effects ofObovatol is known to have various biological activities such as muscle relaxation, anti-gastric ulcer, anti-inflammatory, anti-allergic, and anti-bacterial activities. We examined the effects of JY0691, a newly synthesized obovatol derivative, on the viability and proliferation in rat aortic smooth muscle cells. We also determined the mechanism by which the compound induces cell cycle arrest of the cells. Treatment with JY0691 (0 - 3muM) inhibited proliferation of the cells in a dose-dependent manner without any cytotoxic effect. JY0691 treatment did not decrease the levels of platelet-derived growth factor (PDGF) receptor and several protein kinases which had stimulated by exposing the cells to 25ng/ml PDGF-BB. In contrast, the compound arrested the cell cycle progression in the G(0)/G(1) phase, which was related to the down-regulation of cell cycle regulatory factors such as cyclin D(1)/E, cyclin-dependent kinase (CDK)2/4, and proliferating cell nuclear antigen. Further, JY0691 induced cell cycle arrest in the G(1) phase through up-regulation of p21(cip1), but not of p27(kip1), where p53-mediated signaling was in part involved. Our current findings suggest that JY0691 contains anti-proliferative potential on aortic smooth muscle cells.

• Antiproliferative Action of Cudraflavone B, Isolated From Cudrania tricuspidata, Through the Downregulation of pRb Phosphorylation in Aortic Smooth Muscle Cell Proliferation Signaling.

  Authors: Tack-Joong Kim, Hyeong-Jun Han, Yong Lim, Min-Cheol Song, Jihee Kim, Jin Tae Hong, Hwan-Soo Yoo, Myoung-Yun Pyo, Bang Yeon Hwang, Myoung-Koo Lee, Yeo-Pyo Yun

  Journal of cardiovascular pharmacology. 04/2009;

  Cudrania tricuspidata has been proposed to possess anti-inflammatory, antioxidant, hepatoprotective, and antitumor activities. Although cudraflavone B, isolated from the root bark of C. tricuspidata,Cudrania tricuspidata has been proposed to possess anti-inflammatory, antioxidant, hepatoprotective, and antitumor activities. Although cudraflavone B, isolated from the root bark of C. tricuspidata, has a variety of pharmacological effects, its effects on rat aortic smooth muscle cells (RASMCs) are unclear. In the present study, cudraflavone B was found to inhibit cell proliferation and DNA synthesis in cultured RASMCs. Pretreatment with cudraflavone B (0.1-4 muM) suppressed platelet-derived growth factor-BB (PDGF-BB)-stimulated cell number in a concentration-dependent manner. The inhibition percentages were 19.7%, 36.4%, 52.3%, and 99.1% at concentrations of 0.1, 1, 2, and 4 muM, respectively. Moreover, cudraflavone B inhibited [H]-thymidine incorporation into DNA in RASMCs in response to 25 ng/mL PDGF-BB. PDGF-BB-stimulated DNA synthesis was significantly reduced by 15.9%, 31.7%, 43.1%, and 78.2% at concentrations of 0.1, 1, 2, and 4 muM, respectively. Thus, cudraflavone B blocked the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Furthermore, PDGF-BB-induced phosphorylation of retinoblastoma protein (pRb), the hyperphosphorylation of which is a hallmark of the G1-S transition in the cell cycle, was significantly inhibited by cudraflavone B. Because pRb phosphorylation is regulated by cyclin-dependent kinases (CDKs), we investigated the expression of CDK2, CDK4, cyclin E, and cyclin D1 and the CDK inhibitors p21 and p27. Treatment with cudraflavone B downregulated the cyclins and CDKs and upregulated the expression of p21 and p27, a CDK inhibitor. These findings suggest that cudraflavone B inhibits RASMC proliferation via the induction of p21 and p27 expression and subsequent cell cycle arrest with reduction of pRb phosphorylation at the G1-S phase.

• Antithrombotic and antiplatelet activities of fenofibrate, a lipid-lowering drug.

  Authors: Jung-Jin Lee, Yong-Ri Jin, Ji-Yeon Yu, Tudev Munkhtsetseg, Eun-Seok Park, Yong Lim, Tack-Joong Kim, Myoung-Yun Pyo, Jin Tae Hong, Hwan-Soo Yoo, Youngsoo Kim, Yeo-Pyo Yun

  Atherosclerosis. 03/2009;

  Fenofibrate, a lipid-lowering drug, inhibits hydroxyl-methylglutaryl coenzyme A (HMG-CoA)-reductase activity, thus reducing cholesterol synthesis and increasing the clearance of circulatingFenofibrate, a lipid-lowering drug, inhibits hydroxyl-methylglutaryl coenzyme A (HMG-CoA)-reductase activity, thus reducing cholesterol synthesis and increasing the clearance of circulating LDL-cholesterol via the high affinity receptor system. In addition, fenofibrate has beneficial effects such as the inhibition of tissue factor expression, antithrombotic effect and anti-inflammatory effect. The aim of this study was to investigate the effects of fenofibrate on thrombus formation in vivo and platelet activation in vitro and ex vivo. The carotid arteries of male Sprague-Dawley rats were subjected to chemical injury by FeCl(3), and then blood flow was measured with a blood flowmeter. Fenofibrate (200 and 400mg/kg/day for 1 week) delayed the time to occlusion by 61.3% (p<0.05, n=10) and 90.7% (p<0.01, n=10), respectively. Fenofibrate also significantly inhibited ex vivo platelet aggregations induced by collagen (7.5mug/ml) (p<0.01, n=11) and ADP (10muM) (p<0.01, n=11), respectively, but did not affect coagulation times following activated partial thromboplastin and prothrombin activation, indicating the antithrombotic effect was mediated by its inhibition on platelet activation rather than coagulation system. This antiplatelet activity was revealed to be mediated by the suppression of thromboxane A(2) receptor, cytosolic calcium mobilization, and cyclooxygenase (COX)-1 activity. Taken together, we demonstrate that fenofibrate can significantly inhibit artery thrombus formation in vivo, which may be due to antiplatelet activity via the inhibition of thromboxane A(2) receptor, cytosolic calcium mobilization and COX-1 activity, and the beneficial effect of fenofibrate on cardiovascular system may be also due to its modulation of platelet activation.

• Corynoxeine Isolated from the Hook of Uncaria rhynchophylla Inhibits Rat Aortic Vascular Smooth Muscle Cell Proliferation through the Blocking of Extracellular Signal Regulated Kinase 1/2 Phosphorylation.

  Authors: Tack-Joong Kim, Ju-Hyun Lee, Jung-Jin Lee, Ji-Yeon Yu, Bang Yeon Hwang, Sang-Kyu Ye, Li Shujuan, Li Gao, Myoung-Yun Pyo, Yeo-Pyo Yun

  Biological & pharmaceutical bulletin. 12/2008; 31(11):2073-8.

  The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis andThe proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. Uncaria rhynchophylla is traditional Chinese herb that has been applied to the treatment of convulsive disorders, such as epilepsy, in China. In the present study, we examined whether corynoxeine exerts inhibitory effects on platelet-derived growth factor (PDGF)-BB-induced rat aortic VSMC proliferation and the possible mechanism of such effects. Pre-treatment of VSMCs with corynoxeine (5-50 muM) for 24 h resulted in significant decreases in cell number without any cytotoxicity; the inhibition percentages were 25.0+/-12.5, 63.0+/-27.5 and 88.0+/-12.5% at 5, 20 and 50 muM, respectively. Also, corynoxeine significantly inhibited the 50 ng/ml PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without any cytotoxicity; the inhibitions were 32.8+/-11.0, 51.8+/-8.0 and 76.9+/-7.4% at concentrations of 5, 20 and 50 muM, respectively. Pre-incubation of VSMCs with corynoxeine significantly inhibited PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, whereas corynoxeine had no effects on mitogen-activated protein kinase (MAPK/ERK)-activating kinase 1 and 2 (MEK1/2), Akt, or phospholipase C (PLC)gamma1 activation or on PDGF receptor beta (PDGF-Rbeta) phosphorylation. These results suggest that corynoxeine is a potent ERK1/2 inhibitor of key PDGF-BB-induced VSMC proliferation and may be useful in the prevention and treatment of vascular diseases and restenosis after angioplasty.

• Enhanced release of sphingosine-1-phosphate from hypercholesterolemic platelets: Role in development of hypercholesterolemic atherosclerosis.

  Authors: Dong Ju Son, Hyoung Woo Lee, Hyun Woo Shin, Jung-Jin Lee, Hwan-Soo Yoo, Tack-Joong Kim, Yeo-Pyo Yun, Jin Tae Hong

  Prostaglandins, leukotrienes, and essential fatty acids. 07/2008; 78(6):383-90.

  Although it is well known that sphingosine-1-phosphate (S1P), which induces many biological responses, is present in plasma and is mainly released from activated platelets, little is known whetherAlthough it is well known that sphingosine-1-phosphate (S1P), which induces many biological responses, is present in plasma and is mainly released from activated platelets, little is known whether the release of S1P is increased when platelets are activated in the hypercholesterolemic condition, and what are the roles of increased S1P generation in the development or progression of the atherosclerosis. Results show that 0.5% cholesterol diet for 16 weeks induces platelet hyperaggregability to low doses of agonists as well as development of hypercholesterolemic atherosclerosis in the rabbits. The generation and released level of S1P were significantly increased in the hypersensitized platelets and blood plasma in hypercholesterolemic rabbits. We also demonstrated that S1P increased VSMC proliferation via endothelial differentiation gene (EDG)-1 receptor dependent pathway. Our results indicate that release of S1P from activated platelets was increased by enhanced platelet sensitivity in hypercholesterolemia, which potentiated the ox-LDL-induced VSMC proliferation via EDG-1 receptor pathway.

• Hesperetin, a bioflavonoid, inhibits rat aortic vascular smooth muscle cells proliferation by arresting cell cycle.

  Authors: Yong-Ri Jin, Xiang Hua Han, Yong-He Zhang, Jung-Jin Lee, Yong Lim, Tack-Joong Kim, Hwan-Soo Yoo, Yeo-Pyo Yun

  Journal of cellular biochemistry. 06/2008; 104(1):1-14.

  Diet can be one of the most important factors that influence risks for cardiovascular diseases. Hesperetin, a flavonoid present in grapefruits and oranges, is one candidate that may benefit theDiet can be one of the most important factors that influence risks for cardiovascular diseases. Hesperetin, a flavonoid present in grapefruits and oranges, is one candidate that may benefit the cardiovascular system. In this study, we have investigated the effect of hesperetin on the platelet-derived growth factor (PDGF)-BB-induced proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Hesperetin significantly inhibited 50 ng/ml PDGF-BB-induced rat aortic VSMCs proliferation and [(3)H]-thymidine incorporation into DNA at concentrations of 5, 25, 50, and 100 microM. In accordance with these findings, hesperetin revealed blocking of the PDGF-BB-inducible progression through G(0)/G(1) to S phase of the cell cycle in synchronized cells. Western blot showed that hesperetin inhibited not only phosphorylation of retinoblastoma protein (pRb) and expressions of cyclin A, cyclin D, cyclin E, cyclin-dependent kinase 2 (CDK2) as well as proliferating cell nuclear antigen (PCNA) protein, but also downregulation of cyclin-dependent kinase inhibitor (CKI) p27(kip1), while did not affect CKI p21(cip1), p16(INK4), p53, and CDK4 expressions as well as early signaling transductions such as PDGF beta-receptor, extracellular signal-regulated kinase (ERK) 1/2, Akt, p38, and JNK phosphorylation. These results suggest that hesperetin inhibits PDGF-BB-induced rat aortic VSMCs proliferation via G(0)/G(1) arrest in association with modulation of the expression or activation of cell-cycle regulatory proteins, which may contribute to the beneficial effect of grapefruits and oranges on cardiovascular system.