-
Mi Jin Kim,
Dae Won Kim,
Byung Ryong Lee,
Min Jea Shin,
Young Nam Kim,
Seon Ae Eom,
Byung-Jae Park,
Yoon Shin Cho,
Kyu Hyung Han,
Jinseu Park,
Hyun Sook Hwang,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Diabetes mellitus (DM) is characterized by hyperglycemia. Glyoxalase 1 (GLO) has considerable potential as a possible therapeutic agent for DM. However, the precise action of GLO remains unclear in DM. In this study, we examined the protective effects of GLO protein in a streptozotocin (STZ)-induced diabetes animal model using cell-permeable Tat-GLO protein. Purified Tat-GLO protein was efficiently transduced into RINm5F cells in a time- and dose-dependent manner and protected cells against sodium nitroprusside (SNP)-induced cell death and DNA fragmentation. Furthermore, Tat-GLO protein significantly inhibited blood glucose levels and altered the serum biochemical parameters in STZ-induced diabetic mice. These results demonstrate that transduced Tat-GLO protein protects pancreatic cells by the inhibition of STZ-mediated toxicity. Therefore, Tat-GLO protein could be useful as a therapeutic agent against DM.
Biochemical and Biophysical Research Communications 11/2012; · 2.48 Impact Factor
-
Hoon Jae Jeong,
Dae Won Kim, Mi Jin Kim,
Su Jung Woo,
Hye Ri Kim,
So Mi Kim,
Hyo Sang Jo,
Hyun Sook Hwang,
Duk Soo Kim,
Sung Woo Cho,
Moo Ho Won,
Kyu Hyung Han,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, molecular chaperone and antioxidant activities. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
Experimental and Molecular Medicine 07/2012; · 2.48 Impact Factor
-
Mi Jin Kim,
Dae Won Kim,
Hoon Jae Jeong,
Eun Jeong Sohn,
Min Jea Shin,
Eun Hee Ahn,
Soon Won Kwon,
Young Nam Kim,
Duk-Soo Kim,
Jinseu Park,
Won Sik Eum,
Hyun Sook Hwang,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Parkinson's disease (PD) is caused by various factors such as reactive oxygen species (ROS), dysfunction of mitochondria, and aggregation of misfolded proteins, thereby leading to loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Frataxin (FXN) is associated with iron homeostasis and biogenesis of iron-sulfur clusters in the electron transport chain complex. In this study, we investigated the potential of Tat-FXN to cross the blood-brain barrier (BBB) and protect DA neurons against oxidative stress in a mouse model of PD. Tat-FXN was effectively transduced into SH-SY5Y cells and blocked production of ROS and cleavage of DNA, significantly improving cell survival against 1-methyl-4-phenylpyridinium induced toxicity. In addition, Tat-FXN efficiently penetrated the BBB and exhibited a clear neuroprotective effect on tyrosine hydroxylase-specific DA neurons in the SN in a mice model of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine-induced PD. Therefore, these results suggest that Tat-FXN may provide neuroprotective therapy for ROS related diseases including PD.
Biochimie 07/2012; 94(11):2448-56. · 3.02 Impact Factor
-
Eun Jeong Sohn,
Dae Won Kim, Mi Jin Kim,
Hoon Jae Jeong,
Min Jea Shin,
Eun Hee Ahn,
Soon Won Kwon,
Young Nam Kim,
Duk-Soo Kim,
Kyu Hyung Han,
Jinseu Park,
Hyun Sook Hwang,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress is considered to be involved in a number of human diseases including ischemia. Metallothioneins (MT)-III can protect neuronal cells from the cytotoxicity of reactive oxygen species (ROS). However, MT-III proteins biological function is unclear in ischemia. Thus, we examined the protective effects of MT-III proteins on oxidative stress-induced neuronal cell death and brain ischemic insult.
A human MT-III gene was fused with a protein transduction domain, PEP-1 peptide, to construct a cell permeable PEP-1-MT-III protein. PEP-1-MT-III protein was purified using affinity chromatograph. Transduced PEP-1-MT-III proteins were detected by Western blotting and immunoflourescence. Cell viability and DNA fragmentation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium bromide (MTT) assay and terminal dexoynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Brain ischemic injury was detected with immunohistochemistry.
Purified PEP-1-MT-III proteins transduced into astrocytes in a time- and dose-dependent manner and protected against oxidative stress-induced cell death. Also, transduced PEP-1-MT-III proteins efficiently protected cells against DNA fragmentation. Furthermore, immunohistochemical analysis revealed that PEP-1-MT-III prevented neuronal cell death in the CA1 region of the hippocampus induced by transient forebrain ischemia. We demonstrated that transduced PEP-1-MT-III protein protects against oxidative stress induced cell death in vitro and in vivo.
Transduced PEP-1-MT-III protein has neuroprotective roles as an antioxidant in vitro and in vivo. PEP-1-MT-III protein is a potential therapeutic agent for various human brain diseases such as stroke, Alzheimer's disease, and Parkinson's disease.
Biochimica et Biophysica Acta 06/2012; 1820(10):1647-55. · 4.66 Impact Factor
-
Yeom Pyo Lee,
Dae Won Kim,
Hye Won Kang,
Jae Hyeok Hwang,
Hoon Jae Jeong,
Eun Jeong Sohn, Mi Jin Kim,
Eun Hee Ahn,
Min Jea Shin,
Duk-Soo Kim,
Tae-Cheon Kang,
Oh-Shin Kwon,
Sung-Woo Cho,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Heat shock proteins (HSPs) are a highly conserved family of proteins that are induced in response to various environmental stressors including reactive oxygen species. HSP27 is a chaperone protein with the ability to increase cell survival in response to oxidative stress. Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Although the mechanism of PD remains unclear, oxidative stress is known to be important in its pathogenesis. This study investigated the protective effects of PEP-1-HSP27 on neuronal damage induced by 1-methyl-4-phenyl pyridinium (MPP(+) ) in SH-SY5Y cells and in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-HSP27 rapidly entered the cells and protected them against MPP(+) -induced toxicity by inhibiting the reactive oxygen species levels and DNA fragmentation. Furthermore, transduced PEP-1-HSP27 prevented dopaminergic neuronal cell death in the substantia nigra of MPTP-induced PD mouse models. These results demonstrate that PEP-1-HSP27 provides a potential strategy for therapeutic delivery against various diseases and is a potential tool for the treatment of PD.
FEBS Journal 03/2012; 279(11):1929-42. · 3.79 Impact Factor
-
Dae Won Kim,
Duk-Soo Kim, Mi Jin Kim,
Soon Won Kwon,
Eun Hee Ahn,
Hoon Jae Jeong,
Eun Jeong Sohn,
Suman Dutta,
Soon Sung Lim,
Sung-Woo Cho,
Kil Soo Lee,
Jinseu Park,
Won Sik Eum,
Hyun Sook Hwang,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes. PEP-1-catalase (PEP-1- CAT) was transduced into astrocytes in a time- and dose-dependent manner, reducing cellular toxicity induced by H(2)O(2). Additionally, the group of PEP-1-CAT (+) imipramine showed enhancement of transduction efficiency and therefore increased cellular viability than that of PEP-1-CAT alone. In the gerbil ischemia models, PEP-1-CAT displayed significant neuroprotection in the CA1 region of the hippocampus. Interestingly, PEP-1-CAT (+) imipramine prevented neuronal cell death and lipid peroxidation more markedly than PEP-1-CAT alone. Therefore, our results suggest that imipramine can be used as a drug to enhance the transduction of PEP-1 fusion proteins to cells or animals and their efficacies against various disorders.
BMB reports 10/2011; 44(10):647-52. · 1.72 Impact Factor
-
Woosuk Kim,
Dae Won Kim,
Bich Na Shin,
Dae Young Yoo,
Sung Min Nam, Mi Jin Kim,
Jung Hoon Choi,
Yeo Sung Yoon,
Moo-Ho Won,
Soo Young Choi,
In Koo Hwang
[show abstract]
[hide abstract]
ABSTRACT: Frataxin plays important roles in the mitochondrial respiratory chain and in the differentiation of neurons during early development. In this study, we observed the effects of frataxin on cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus. For this, we constructed an expression vector, PEP-1, that was fused with frataxin to create a PEP-1-frataxin fusion protein that easily penetrated frataxin into the blood-brain barrier. Three mg/kg PEP-1-frataxin was intraperitoneally administered to mice once a day for 2 weeks. The administration of PEP-1 alone did not result in any significant changes in the number of Ki67-positive cells and doublecortin (DCX)-immunoreactive neuroblasts in the mouse dentate gyrus. However, the administration of PEP-1-frataxin significantly increased the number of Ki67-positive cells and DCX-immunoreactive neuroblasts in the mouse dentate gyrus. In addition, PEP-1-frataxin significantly reduced 4-hydroxynonenal protein levels and malondialdehyde formation, while Cu, Zn-superoxide dismutase protein levels were maintained. These results suggest that frataxin effectively increased cell proliferation and neuroblast differentiation by decreasing lipid peroxidation in the dentate gyrus.
Neurochemical Research 09/2011; 36(12):2452-8. · 2.24 Impact Factor
-
Soon Won Kwon,
Eun Jeong Sohn,
Dae Won Kim,
Hoon Jae Jeong, Mi Jin Kim,
Eun Hee Ahn,
Young Nam Kim,
Suman Dutta,
Duk-Soo Kim,
Jinseu Park,
Won Sik Eum,
Hyun Sook Hwang,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe(2+)), is up-regulated by several cellular stress and cell injuries, including inflammation, ischemia and hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein transduction domain that is able to deliver exogenous molecules to living cells or tissues, would facilitate HO-1 delivery to target cells and tissues, and thereby effectively exert a therapeutically useful response against inflammation. Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were transduced into Raw 264.7 cells in time- and dose-dependent manners, and were stably maintained in the cells for about 60h. In addition, fluorescence analysis revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into the cytoplasm of cells, while HO-1 proteins failed to be transduced. In lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins effectively inhibited the overexpression of pro-inflammatory mediators and cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can be used as a therapeutic molecule against reactive oxygen species-related inflammatory diseases.
Biochemical and Biophysical Research Communications 07/2011; 411(2):354-9. · 2.48 Impact Factor
-
So Young Kim,
Eun Jeong Sohn,
Dae Won Kim,
Hoon Jae Jeong, Mi Jin Kim,
Hye Won Kang,
Min Jea Shin,
Eun Hee Ahn,
Soon Won Kwon,
Young Nam Kim,
Hyung Joo Kwon,
Tae-Yoon Kim,
Kil Soo Lee,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Immunophilin, FK506-binding protein 12 (FK506BP), is a receptor protein for the immunosuppressive drug FK506 by the FK506BP/FK506 complex. However, the precise function of FK506BP in inflammatory diseases remains unclear. Therefore, we examined the protective effects of FK506BP on atopic dermatitis (AD) in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-induced HaCaT cells and 2,4-dinitrofluorobenzene-induced AD-like dermatitis in Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice using a cell-permeable PEP-1-FK506BP. Transduced PEP-1-FK506BP significantly inhibited the expression of cytokines, as well as the activation of NF-κB and mitogen-activated protein kinase (MAPK) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, topical application of PEP-1-FK506BP to NC/Nga mice markedly inhibited AD-like dermatitis as determined by a histological examination and assessment of serum IgE levels, as well as cytokines and chemokines. These results indicate that PEP-1-FK506BP inhibits NF-κB and MAPK activation in cells and AD-like skin lesions by reducing the expression levels of cytokines and chemokines, thus suggesting that PEP-1-FK506BP may be a potential therapeutic agent for AD.
Journal of Investigative Dermatology 03/2011; 131(7):1477-85. · 6.31 Impact Factor
-
So Young Kim,
Hoon Jae Jeong,
Dae Won Kim, Mi Jin Kim,
Jae Jin An,
Eun Jeong Sohn,
Hye Won Kang,
Min Jea Shin,
Eun Hee Ahn,
Soon Won Kwon,
Duk-Soo Kim,
Sung-Woo Cho,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: FK506 binding protein 12 (FK506BP) is an immunophilin that acts as a receptor for the immunosuppressant drug FK506. Although the precise action of FK506BP remains unclear, it has emerged as a potential drug target for several inflammatory diseases. This study investigated the protective effects of FK506BP on inflammation in vitro and in vivo using protein transduction. A cell-permeable expression vector PEP-1-FK506BP was constructed. Lipopolysaccharide (LPS)- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated Raw 264.7 cells and ICR mice were treated with PEP-1-FK506BP. The expression of inflammatory response enzymes and cytokines was analyzed by Western blot, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay. PEP-1-FK506BP efficiently transduced into Raw 264.7 cells and markedly inhibited the expression levels of cyclooxygenase-2 as well as pro-inflammatory cytokines. Furthermore, transduced PEP-1-FK506BP significantly reduced activation of nuclear factor-kappa B (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the cells, whereas PEP-1-FK506BP reduced phosphorylation of p38 and extracellular signal-regulated kinase (ERK) in the animal models. These results indicate that PEP-1-FK506BP inhibits inflammatory response cytokines and enzymes by blocking NF-κB and MAPK including the phosphorylation of p38 and/or ERK MAPK in vitro and in vivo, suggesting that PEP-1-FK506BP may be a therapeutic agent against inflammatory skin diseases.
Immunobiology 12/2010; 216(7):771-81. · 3.20 Impact Factor
-
Mi Jin Kim,
Dae Won Kim,
Ki-Yeon Yoo,
Eun Jeong Sohn,
Hoon Jae Jeong,
Hye Won Kang,
Min Jea Shin,
Eun Hee Ahn,
Jae Jin An,
Soon Won Kwon,
Young Nam Kim,
Moo Ho Won,
Sung-Woo Cho,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Reactive oxygen species (ROS) actively contribute to the development of a number of human diseases including ischemia. In response to oxidative stress, frataxin has a significant ability to improve cell survival though its biological function is unclear in relation to ischemia. To explore frataxin's role in protecting against ischemic cell death, we constructed PEP-1-Frataxin cell-permeable fusion protein. In a dose- and time-dependent manner PEP-1-Frataxin rapidly transduced into astrocyte cells and protected them against oxidative stress-induced cell death. Further, using an animal model, immunohistochemical analysis revealed that PEP-1-Frataxin prevented neuronal cell death in the CA1 region of the hippocampus induced by transient forebrain ischemia. These results demonstrate that transduced PEP-1-Frataxin protects against cell death in vitro and in vivo, suggesting that transduction of PEP-1-Frataxin could be useful as a therapeutic agent for various human diseases related to oxidative stress.
Journal of the neurological sciences 11/2010; 298(1-2):64-9. · 2.32 Impact Factor
-
Sun Hwa Lee,
Hoon Jae Jeong,
Dae Won Kim,
Eun Jeong Sohn, Mi Jin Kim,
Duk Soo Kim,
Tae Cheon Kang,
Soon Sung Lim,
Il Jun Kang,
Sung Woo Cho,
Kil Soo Lee,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Though protein transduction domains (PTDs) are well known for the delivery of exogenous therapeutic proteins into living cells, the overall low efficiency of transduction is a serious obstacle. We investigated the effect of bog blueberry anthocyanins (BBA) on protein transduction efficiency and found that BBA enhanced the transduction efficiencies of Tat-SOD fusion protein into HeLa cells and mice skin. The enzymatic activities in the cells and skin tissue in the presence of BBA were markedly increased compared to controls. Further, BBA did not demonstrate any cell toxicity at various concentrations. Although the mechanism is not fully understood, we suggest that BBA might alter the conformation of the membrane, which would indicate that BBA can be used as a protein transduction enhancer for the efficient delivery of therapeutic proteins for a variety of disorders.
BMB reports 08/2010; 43(8):561-6. · 1.72 Impact Factor
-
Dae Won Kim,
Sun Hwa Lee,
Min Seop Jeong,
Eun Jeong Sohn, Mi Jin Kim,
Hoon Jae Jeong,
Jae Jin An,
Sang Ho Jang,
Moo Ho Won,
In Koo Hwang,
Sung-Woo Cho,
Tae-Cheon Kang,
Kil Soo Lee,
Jinseu Park,
Ki-Yeon Yoo,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Reactive oxygen species (ROS) have been implicated in the pathogenesis of ischemic brain injury. Sensitive to apoptosis gene (SAG) is a RING-finger protein that exhibits antioxidant activity against a variety of redox reagents. However, the protective effect of SAG in brain ischemic injury is unclear. Here, we investigated the protective effects of a Tat-SAG fusion protein against cell death and ischemic insult. When Tat-SAG fusion protein was added to the culture medium of astrocytes, it rapidly entered the cells and protected them against oxidative stress-induced cell death. Immunohistochemical analysis revealed that, when Tat-SAG fusion protein was intraperitoneally injected into gerbils, wild-type Tat-SAG prevented neuronal cell death in the CA1 region of the hippocampus in response to transient forebrain ischemia. In addition, wild-type Tat-SAG fusion protein decreased lipid peroxidation in the brain compared with mutant Tat-SAG- or vehicle-treated animals. Our results demonstrate that Tat-SAG fusion protein is a tool for the treatment of ischemic insult and it can be used in protein therapy for various disorders related to ROS, including stroke.
Free radical biology & medicine 04/2010; 48(7):969-77. · 5.42 Impact Factor
-
Min Jung Lee,
Dae Won Kim,
Yeom Pyo Lee,
Hoon Jae Jeong,
Hye Won Kang,
Min Jae Shin,
Eun Jeong Sohn, Mi Jin Kim,
Sang Ho Jang,
Tae-Cheon Kang,
Moo Ho Won,
Bon-Hong Min,
Sung-Woo Cho,
Kil Soo Lee,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Arginine deiminase (ADI), an arginine-degrading enzyme, has anti-proliferative and anti-tumor activities and is capable of inhibiting the production of nitric oxide (NO). Modulation of nitric oxide (NO) production is considered a promising approach for the treatment of various diseases including cancer, inflammation and neuronal disorders. In this study, an ADI gene was fused with an HIV-1 Tat peptide in a bacterial expression vector to produce an genetic in-frame Tat-ADI fusion protein. When added exogenously to the culture media, the expressed and purified Tat-ADI fusion proteins were efficiently transduced into macrophage Raw 264.7 cells in a time- and dose-dependent manner. Furthermore, transduced Tat-ADI fusion proteins markedly increased cell viability in cells treated with lipopolysaccharide (LPS). This increase in viability was mediated by an inhibition of NO production. These results suggest that this Tat-ADI fusion protein can be used in protein therapies of NO-related disorders such as cancer, inflammation and neuronal diseases.
BMB reports 06/2009; 42(5):286-92. · 1.72 Impact Factor
-
Jae Jin An,
Yeom Pyo Lee,
Dae Won Kim,
Eun Joung Sohn,
Hoon Jae Jeong,
Hye Won Kang,
Min Jae Shin, Mi Jin Kim,
Eun Hee Ahn,
Sang Ho Jang,
Jung Hoon Kang,
Tae-Cheon Kang,
Moo Ho Won,
Oh-Shin Kwon,
Sung-Woo Cho,
Kil Soo Lee,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Familial Amyotrophic lateral sclerosis (FALS) is a progressive neurodegenetative disorder induced by mutations of the SOD1 gene. Heat shock protein 27 (HSP27) is well-defined as a stress-inducible protein, however the its role in ALS protection has not yet been established. To investigate the role HSP27 may have in SOD1 mutant-mediated apoptosis, human SOD1 or HSP27 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame fusion protein, which was then transduced into cells. We found the purified PEP-1-HSP27 fusion proteins can be transduced efficiently into neuronal cells and protect against cell death by enhancing mutant SOD1 activity. Moreover, transduced PEP-1-HSP27 efficiently prevents protein aggregation produced by oxidative stress. These results suggest that transduced HSP27 fusion protein may be explored as a potential therapeutic agent for FALS patients.
BMB reports 04/2009; 42(3):136-41. · 1.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ICAM-3 interacts with LFA1, and is involved in the intercellular adhesion of leukocytes as well as in the mainenance of cell survival. It has also been suggested to induce cancer cell proliferation but the precise signaling pathway is unclear. The aim of this study was to determine the ICAM-3-activated downstream pathway in H1299 lung cancer cells. The level of ICAM-3-induced cell growth was examined using BrdU incorporation, which is a colony-forming assay, FACS analysis, and cell counting. The results showed that ICAM-3 expression induces cancer cell proliferation. In addition, FAK, Akt, PDK1, GSK-3beta, BAD, and PTEN were phosphorylated by ICAM-3-overexpression, resulting in enhanced cell proliferation. In conclusion, ICAM-3 expression induces cancer cell proliferation, and an increase in ICAM-3 expression can contribute to cancer progression.
Cancer Letters 08/2006; 239(1):103-10. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ribosomal proteins not only act as components of the translation apparatus but also regulate cell proliferation and apoptosis. A previous study reported that MRPL41 plays an important role in p53-dependent apoptosis. It also showed that MRPL41 arrests the cell cycle by stabilizing p27(Kip1) in the absence of p53. This study found that MRPL41 mediates the p21(WAF1/CIP1)-mediated G1 arrest in response to serum starvation. The cells were released from serum starvation-induced G1 arrest via the siRNA-mediated blocking of MRPL41 expression. Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21(WAF1/CIP1) and p27(Kip1) levels under the growth inhibitory conditions.
Biochemical and Biophysical Research Communications 01/2006; 338(2):1179-84. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The p53 protein arrests the cell cycle at the G1 phase when stabilized by the interaction between ribosomal proteins and HDM2 under growth-inhibitory conditions. Meanwhile, p53, when translocated to the mitochondria in response to cell death signals, induces apoptosis via transcription-independent mechanisms. In this report, we demonstrate that the mitochondrial ribosomal protein L41 (MRPL41) enhances p53 stability and contributes to p53-induced apoptosis in response to growth-inhibitory conditions such as actinomycin D treatment and serum starvation. An analysis of MRPL41 expression in paired normal and tumor tissues revealed lower expression in tumor tissue. Ectopic MRPL41 expression resulted in inhibition of the growth of cancer cells in tissue culture and tumor growth in nude mice. We discovered that MRPL41 protein is localized in the mitochondria, stabilizes the p53 protein, and enhances its translocation to the mitochondria, thereby inducing apoptosis. Interestingly, in the absence of p53, MRPL41 stabilizes the p27(Kip1) protein and arrests the cell cycle at the G1 phase. These results suggest that MRPL41 plays an important role in p53-induced mitochondrion-dependent apoptosis and MRPL41 exerts a tumor-suppressive effect in association with p53 and p27 (Kip1).
Molecular and Cellular Biology 09/2005; 25(15):6603-16. · 5.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ribosomal proteins not only act as components of the translation apparatus but also regulate cell proliferation and apoptosis. A previous study reported that MRPL41 plays an important role in p53-dependent apoptosis. It also showed that MRPL41 arrests the cell cycle by stabilizing p27Kip1 in the absence of p53. This study found that MRPL41 mediates the p21WAF1/CIP1-mediated G1 arrest in response to serum starvation. The cells were released from serum starvation-induced G1 arrest via the siRNA-mediated blocking of MRPL41 expression. Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21WAF1/CIP1 and p27Kip1 levels under the growth inhibitory conditions.
Biochemical and Biophysical Research Communications.
-
Dae Won Kim,
Hoon Jae Jeong,
Hye Won Kang,
Min Jea Shin,
Eun Jeong Sohn, Mi Jin Kim,
Eun Hee Ahn,
Jae Jin An,
Sang Ho Jang,
Ki-Yeon Yoo,
Moo Ho Won,
Tae-Cheon Kang,
In Koo Hwang,
Oh-Shin Kwon,
Sung-Woo Cho,
Jinseu Park,
Won Sik Eum,
Soo Young Choi
[show abstract]
[hide abstract]
ABSTRACT: Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by reactive oxygen species (ROS). Ischemia is characterized by both oxidative stress and changes in the antioxidant defense system. Catalase (CAT) and superoxide dismutase (SOD) are major antioxidant enzymes by which cells counteract the deleterious effects of ROS. To investigate the protective effects of CAT, we constructed PEP-1–CAT cell-permeative expression vectors. When PEP-1–CAT fusion proteins were added to the culture medium of neuronal cells, they rapidly entered the cells and protected them against oxidative stress-induced neuronal cell death. Immunohistochemical analysis revealed that PEP-1–CAT prevented neuronal cell death in the hippocampus induced by transient forebrain ischemia. Moreover, we showed that the protective effect of PEP-1–CAT was observed in neuronal cells treated with PEP-1–SOD. Therefore, we suggest that transduced PEP-1–CAT and PEP-1–SOD fusion proteins could be useful as therapeutic agents for various human diseases related to oxidative stress, including stroke.
Free Radical Biology and Medicine.
