-
[show abstract]
[hide abstract]
ABSTRACT: Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma cells were treated with artemether at various concentrations and shRNA interfering technology was employed to silence the expression of VCAM-1. Cell viability, migration, invasiveness and apoptosis were assessed with MTT, wound healing, Transwell and Annexin V-FITC/PI staining. The expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and phosphorylated Akt (p-Akt) was checked by Western blot assay. Results showed that artemether and shRNA-VCAM-1 not only significantly inhibited the migration, invasiveness and expression of MMP-2/9 and p-Akt, but also promoted the apoptosis of U87 cells. Combined treatment of both displayed the maximum inhibitory effects on the malignant biological behavior of glioma cells. Our work revealed the potential therapeutic effects of artemether and antiVCAM-1 in the treatments of gliomas.
PLoS ONE 01/2013; 8(4):e60834. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The calcium-activated potassium channel (K (Ca) channel) activator, NS1619, has been shown to selectively and time-dependently increase the permeability of the blood-tumor barrier (BTB) by downregulating the expression of tight junction (TJ) protein. However, the role of signaling cascades in this process has not been precisely elucidated. This study was performed to determine the role of signaling cascades involving reactive oxygen species (ROS)/RhoA/PI3K/PKB in increasing the permeability of the BTB induced by NS1619. Using an in vitro BTB model and selective inhibitors of signaling pathways, we investigated whether ROS/RhoA/PI3K/PKB pathway plays a key role in the process of the increase in BTB permeability induced by NS1619. The results revealed that the BTB permeability was increased and the expression of TJ proteins were significantly decreased by NS1619, and selective inhibitors of identified signaling pathways reversed the observed alterations. Moreover, the significant increases in ROS, RhoA activity, and PKB phosphorylation after NS1619 administration were observed, which were partly inhibited by N-2-mercaptopropionyl glycine or C3 exoenzyme or LY294002 pretreatment. The present study demonstrates that the activation of signaling cascades involving ROS/RhoA/PI3K/PKB in rat brain microvascular endothelial cells was required for the increase in BTB permeability induced by NS1619.
Journal of Molecular Neuroscience 05/2012; 48(1):302-12. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The tropism of bone marrow-derived mesenchymal stem cells (BMSCs) toward gliomas has been shown by in vitro and in vivo assays. This study was carried out to evaluate the role of vascular cell adhesion molecule-1 (VCAM-1) in the migration of BMSCs towards glioma and the effect of glioma cells on the VCAM-1 expression of BMSCs. BMSCs were isolated according to their adherence to plastic. The tropism of BMSCs toward C6 and U87 glioma and the role of VCAM-1 in this migration were analyzed by in vitro migration assay, separately. Reverse transcription-polymerase chain reaction, immunofluorescence, and Western blot were employed to assess VCAM-1 expression of BMSCs when they were incubated by the conditioned mediums (CM) of C6 or U87 glioma cells. Data revealed that C6 and U87 glioma cells promote the migration of BMSCs, which could be blocked by a VCAM-1-neutralizing antibody. Moreover, VCAM-1 expression of BMSCs was elevated by the incubation of their CM. The results also demonstrated that LY294002, an inhibitor of phosphoinositide-3-kinase (PI3K), significantly inhibited the glioma-induced upregulation of VCAM-1 on BMSCs. These findings suggested that glioma-induced change in VCAM-1 expression of BMSCs may play an important role in their tropism towards glioma, and PI3K is associated with the signal transduction of this process.
Journal of Molecular Neuroscience 05/2012; 48(1):127-35. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: DNA topoisomerase II alpha (Topo-IIα) is an essential nuclear enzyme with its up-regulation demonstrated in different tumors. This study is to evaluate the expression of Topo-IIα in glioblastoma cancer stem cells (CSCs) and its effects on cell proliferation and apoptosis. We observed the expression differences of Topo-IIα gene transcript in CSCs and non-CSCs in glioblastoma cell line U87 by quantitative real-time PCR and western blot; we silenced Topo-IIα expression in U87 CSCs using Topo-IIα-specific siRNA to investigate the role of Topo-IIα in cell proliferation, cell cycle, and apoptosis. We found higher expression of Topo-IIα in CSCs than in non-CSCs. After using Topo-IIα-specific siRNA to silence the expression of Topo-IIα gene, we observed decreasing cell proliferation, cell cycle arrest, and induction of apoptosis in CSCs, which suggest that Topo-IIα contributes to both cell proliferation and/or cell survival. Topo-IIα may be a novel marker of cell proliferation and/or survival factor in glioblastoma CSCs. It may be a potential target that will open up new opportunities to develop therapeutic strategies for gliomas.
Neuroscience Letters 05/2012; 518(2):138-43. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our previous studies have demonstrated that both the RhoA/Rho kinase and the protein kinase C (PKC) signaling pathways are involved in the low-dose endothelial monocyte-activating polypeptide-II (EMAP-II)-induced blood-tumor barrier (BTB) opening. In the present study, an in vitro BTB model was used to investigate which isoforms of PKC were involved in this process as well as the interactions between the RhoA/Rho kinase and the PKC signaling pathways. Our results showed that EMAP-II-activated PKC-α, β, and ζ and induced translocations of them from the cytosolic to the membrane fractions of rat brain microvascular endothelial cells. The EMAP-II-induced alterations in BTB permeability and tight junction (TJ) protein expression were partially blocked by GÖ6976, the inhibitor of PKC-α/β, and PKC-ζ pseudosubstrate inhibitor (PKC-ζ-PI). Meanwhile, we observed that GÖ6976 partly inhibited the EMAP-II-induced rearrangement of actin cytoskeleton as well as phosphorylation of myosin light chain and cofilin, whereas PKC-ζ-PI had no effect on these above-mentioned changes induced by EMAP-II. Also, our data revealed that inhibition of RhoA or inhibition of Rho kinase significantly diminished the activities and the translocations of PKC-α and PKC-β induced by EMAP-II, whereas PKC-ζ was unaffected. However, inhibition of PKC-α/β or inhibition of PKC-ζ did not cause any changes in the RhoA and Rho kinase activities. The effects of EMAP-II on BTB permeability and TJ proteins expression were completely blocked by inhibition of both RhoA and PKC-ζ, whereas inhibition of both RhoA and PKC-α/β had an effect similar to that of inhibition of RhoA alone. In summary, this study demonstrates for the first time that three PKC isoforms, PKC-α, β, and ζ, are involved in the EMAP-II-induced BTB opening. It is PKC-α/β, but not PKC-ζ, which serves as the downstream target for RhoA and Rho kinase, suggesting that EMAP-II induces BTB opening via the RhoA/Rho kinase/PKC-α/β signaling pathways. However, PKC-ζ is involved in this process by other mechanisms.
Journal of Molecular Neuroscience 04/2012; 48(1):291-301. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Low-frequency ultrasound (LFU) irradiation under certain acoustic intensity can increase blood-brain barrier permeability non-invasively and reversibly. The aim of this study was to find out the effect of LFU irradiation on blood-tumor barrier (BTB) permeability in rat C6 glioma model and the possible mechanism. In this research, Evans blue and H&E staining were used to evaluate the optimal parameter of LFU to open the BTB without damaging the normal brain tissue. Transmission electron microscopy was used to observe the changes of the number of pinocytotic vesicles in cerebral or glioma microvascular endothelial cells. The phosphorylation of tyrosine kinase Src, caveolin-1, and caveolin-2 was detected by western blot. The distribution and expressing levels of caveolae proteins, caveolin-1 and caveolin-2, were detected by immunohistochemical and immunofluorescent staining, RT-PCR, and western blot. Our research data showed that, in rat C6 glioma model, LFU irradiation at a frequency of 1 MHz, a power of 12 mW, and exposure time of 20 s induced the increase of BTB permeability temporally, which reached a peak at 1.5 h, then decreased and restored to normal level at 12 h after LFU irradiation. In the glioma microvascular endothelial cells of rat glioma model, LFU irradiation induced a significant increase of the pinocytotic vesicles' density. The phosphorylation of Src, caveolin-1, and caveolin-2 began to increase at 0.5 h and reached a maximum at 1 h. Immunohistochemical and immunofluorescent staining showed that caveolin-1 and caveolin-2 were co-localized in the glioma microvascular endothelial cells and glioma cells. The mRNA and protein expression levels of caveolin-1 and caveolin-2 were up-regulated, reached the peak value at 1.5 h, and re-normalized at 12 h after LFU irradiation. These results demonstrated that LFU irradiation increased BTB permeability by promoting transcellular transport in glioma microvascular endothelial cells. The phosphorylation of tyrosine kinase Src, caveolin-1, caveolin-2 and up-regulation of caveolin-1 and caveolin-2 were involved in LFU-induced caveolae-mediated endocytosis.
Journal of Molecular Neuroscience 04/2012; 48(1):281-90. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ObjectiveTo investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats
with Alzheimer’s disease (AD).
MethodsThe rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received
OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1
μL (10 μg/μL) amyloid-beta peptide 1–40(Aβ1–40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological
method, respectively.
ResultsThe escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P < 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency
stimulation (HFS), compared with that in OVX group (P < 0.01).
ConclusionERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in
AD rats.
目的探讨雌二醇对阿尔茨海默病(Alzheimer’s disease, AD)大鼠的学习记忆能力及长时程增强(long-term potentiation, LTP)的影响。
方法大鼠随机分成卵巢切除 (ovariectomy, OVX)组和雌激素替代治疗(estrogen replace treatment, ERT)组。 两组大鼠均接受卵巢切除手术, ERT组大鼠随后接受雌激素替代治疗。 手术2周后, 两组大鼠海马内立体定位单侧注射1
μL Aβ1–40 (10 μg/μL), 建立AD模型。 运用水迷宫实验检测大鼠的学习和记忆能力, 并进行LTP记录和比较。
结果OVX组AD大鼠的水迷宫逃避潜伏期相较于ERT组明显延长(P < 0.05)。 此外, 高频刺激(high frequence stimulation, HFS) 30 min后与HFS刺激前相比, ERT组LTP增加的幅值明显高于OVX组(P < 0.05)。
结论雌激素替代治疗能改善AD大鼠的认知功能, 调整LTP及突触可塑性。
Keywordsestradiol-long-term potentiation-learning and memory-rat-Alzheimer’s disease
关键词雌二醇-长时程增强-学习和记忆-大鼠-阿尔茨海默病
Neuroscience Bulletin 04/2012; 26(2):133-139. · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Curcumin, the active component of turmeric, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about its anti-tumor mechanism in small cell lung cancer (SCLC). In this study, we found that curcumin can inhibit SCLC cell proliferation, cell cycle, migration, invasion and angiogenesis through suppression of the STAT3. SCLC cells were treated with curcumin (15 µmol/L) and the results showed that curcumin was effective in inhibiting STAT3 phosphorylation to downregulate of an array of STAT3 downstream targets ,which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion. Curcumin also suppressed the expression of proliferative proteins (Survivin, Bcl-X(L) and Cyclin B1), and invasive proteins (VEGF, MMP-2, MMP-7 and ICAM-1). Knockdown of STAT3 expression by siRNA was able to induce anti-invasive effects in vitro. In contrast, activation of STAT3 upstream of interleukin 6 (IL-6) leads to the increased cell proliferation ,cell survival, angiogenesis, invasion, migration and tumor growth. Our findings illustrate the biologic significance of IL-6/JAK/STAT3 signaling in SCLC progression and provide novel evidence that the pathway may be a new potential target for therapy of SCLC. It was concluded that curcumin is a potent agent in the inhibition of STAT3 with favorable pharmacological activity,and curcumin may have translational potential as an effective cancer therapeutic or preventive agent for SCLC.
PLoS ONE 01/2012; 7(5):e37960. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to determine whether the expressions of MMP-7 and MMP-14 are associated with the ERK 1/2 signaling pathway in human brain gliomas of different pathological grades. Immunohistochemistry and western blot methods were used to determine the expressions of MMP-7, MMP-14 and the phosphorylation status of ERK1/2 in 73 cases of human brain glioma specimens and two cases of normal brain tissues. Results indicated that the protein expression levels of MMP-7, MMP-14 and ERK1/2 phosphorylation level were all elevated with the increasing pathological grades in brain glioma tissues, and correlation assay indicated that the level of ERK1/2 phosphorylation was positively correlated with protein expression levels of MMP-7 and MMP-14 in gliomas of different pathological grades respectively. Moreover, the impact of ERK1/2 inhibitor U0126 on the expressions of MMP-7 and MMP-14 was examined in human U87 glioma cells by western blot analysis. The expressions of MMP-7 and MMP-14 were significantly decreased in human U87 glioma cells after treatment with ERK1/2 inhibitor U0126. The above results suggest that the expressions of MMP-7 and MMP-14 may be associated with activation of ERK1/2 signaling pathway in human brain gliomas of different pathological grades.
Medical Oncology 12/2011; 28 Suppl 1:S433-8. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial monocyte-activating polypeptide-II (EMAP-II) increases blood-tumor barrier (BTB) permeability by inducing alterations in the tight junction (TJ) complex between brain endothelial cells. In the present study, an in vitro BTB model was used to search for the interacting and functional cell surface molecule of EMAP-II as well as the signaling pathway involved in the EMAP-II-induced BTB hyperpermeability. Our results revealed that EMAP-II-induced increase in BTB permeability and down-regulation of TJ-related proteins occludin and ZO-1 were associated with its binding to ATP synthase α subunit (α-ATP synthase) on the surface of rat brain microvascular endothelial cells (BMECs). In addition, we observed that EMAP-II administration activated protein kinase C (PKC) and induced the translocation of PKC from the cytosolic to the membrane fraction of BMECs. The effects of EMAP-II on BTB permeability as well as expression levels of occludin and ZO-1 in BMECs were significantly diminished by H7, the inhibitor of PKC. In summary, these data suggest that EMAP-II increases BTB permeability through α-ATP synthase on the surface of BMECs, and PKC signaling pathway might be involved in this process.
Journal of Molecular Neuroscience 10/2011; 47(2):408-17. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Curcumin (diferuloylmethane), an active component of the spice turmeric, induces apoptosis in several types of malignancies. However, little is known about its anticancer activity in small cell lung cancer (SCLC). SCLC represents a highly malignant and particularly aggressive form of cancer, with early and widespread metastases and a poor prognosis. In this study, we found that curcumin does not activate caspase-8 cleavage or alter the expression of apoptotic receptors FAS and TRAIL in NCI-H446 cells, suggesting that curcumin-induced apoptosis is not associated with death receptor-mediated pathways in these cells. Instead, curcumin caused apoptosis by increasing Bax expression while decreasing the expression of Bcl-2 and Bcl-xL. Curcumin induced a rapid decrease in mitochondrial membrane potential and the release of cytochrome c into the cytosol, followed by activation of caspase-9 and caspase-3. In addition, curcumin-induced apoptosis was accompanied by an increase of intracellular reactive oxygen species (ROS) level. These results indicated that a ROS-mediated mitochondrial pathway played an important role in the process of curcumin-induced apoptosis of human SCLC NCI-H446 cells.
DNA and cell biology 06/2011; 31(2):139-50. · 2.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of the present study was to determine the potential for RhoA/ROCK signaling to play a role in endothelial-monocyte-activating polypeptide (EMAP) II-induced increase in blood-tumor barrier (BTB) permeability in rat brain microvascular endothelial cells (RBMECs). In the present study, we used an in vitro BTB model, a RhoA inhibitor (C3 exoenzyme) and a ROCK inhibitor (Y27632) to determine whether RhoA/ROCK pathway play a role in the process of TJ disassembly, stress fiber formation, MLC and cofilin phosphorylation, as well as increase of BTB permeability induced by EMAP II. The results revealed that BTB permeability was increased by EMAP II induction, and C3 exoenzyme or Y27632 could partially inhibit the EMAP II-induced increase of BTB permeability. The significant down-regulations in tight junction (TJ)-associated proteins occludin, claudin-5 and ZO-1 and stress fiber formation by EMAP II administration were observed, which were partly prevented by C3 exoenzyme or Y27632 pretreatment. Moreover, the significant increases in RhoA activity, myosin light chain (MLC) and cofilin phosphorylation by EMAP II administration were observed, MLC and cofilin phosphorylation were partly inhibited by C3 exoenzyme or Y27632 pretreatment. The present study demonstrates that the activation of RhoA/ROCK signaling in RBMECs was required for the increase of BTB permeability and these effects are related with the ability for RhoA/ROCK to mediate TJ disassembly and stress fiber formation by phosphorylating cofilin and MLC.
Journal of Molecular Neuroscience 06/2011; 46(3):666-76. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was performed to determine whether low frequency ultrasound (LFU) irradiation, Papaverine (PA) infusion and combination LFU irradiation with PA infusion opened the blood-tumor barrier (BTB) by affecting tight junctions (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin and caludin-5. In a rat brain glioma model, we found that the mRNA and protein expression levels of ZO-1, occludin and claudin-5 were decreased by LFU irradiation and PA infusion. LFU-induced and PA-induced decrease of ZO-1, occludin and claudin-5 was further decreased after combining LFU irradiation with PA infusion. Immunohistochemistry assay showed that the decreased expression of ZO-1, occludin and claudin-5 was the most obvious in the tumor capillaries. Meanwhile, Evans blue assay showed that the permeability of BTB was increased, and transmission electron microscopy (TEM) indicated that TJ was opened. This led to the conclusion that LFU irradiation and PA infusion together can open the BTB by paracellular pathway. Significantly down-regulated expression levels of ZO-1, occludin and claudin-5 might be one of the molecular mechanisms of combining LFU and PA enhancing the permeability of BTB.
Journal of Neuro-Oncology 04/2011; 102(2):213-24. · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was performed to investigate the mechanism of the blood-brain tumor-barrier (BTB) permeability increase, which was induced by NS1619, a selective K(Ca) channel activator. Using a rat brain glioma (C6) model, we exam the expression of ZO-1 and occludin in mRNA and protein level at different time point after intracarotid infusion of NS1619 (30 μg/kg/min) to tumor sites via RT-PCR and Western blot analysis. The mRNA and protein expression of ZO-1 and occludin had no great change before infusion and began to decrease significantly after 2 h NS1619 infusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of BTB permeability and malonaldehyde (MDA) level induced by NS1619. This led to the conclusion that NS1619 could time-dependently increase the BTB permeability by down-regulating the expression of tight junction protein, and this effect could be reversed by ROS.
Neuroscience Letters 02/2011; 493(3):140-4. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was performed to determine whether minoxidil sulfate (MS), a selective Adenosine 5'-triphosphate-sensitive potassium channel (K (ATP) channel) activator, has an effect on the expression of caveolin-1 in the rat's brain tumor tissue. Using a rat brain glioma (C6) model, we found that the expression of caveolin-1 protein at tumor sites was greatly increased after intracarotid infusion of MS at a dose of 30 μg/kg/min for 15, 30, and 60 min via Western blot analysis. And the peak value of the caveolin-1 expression was observed in rats with glioma after 15 min of MS perfusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG). In addition, MPG also significantly inhibited the increase of blood-brain tumor barrier (BTB) permeability which was induced by MS. This led to the conclusion that the MS-induced BTB permeability increase may be related to the accelerated formation of caveolin-1 protein, and could be mediated by ROS.
Cellular and Molecular Neurobiology 02/2011; 31(4):629-34. · 1.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The early diagnosis and treatment of non-small cell lung cancer (NSCLC) in patients with subclinical pleural metastasis is currently a challenge. In an effort to establish a method for the diagnosis and treatment of these patients, we conducted a single-blind study during which intraoperative pleural lavage cytology (PLC) was performed in 164 patients with NSCLC without obvious pleural effusion. Stromal cell-derived factor-1 (SDF-1) serum concentrations were analyzed using enzyme-linked immunoassay on day 1 prior to tumor resection and on day 7 postoperatively. Western blot analysis was used for the detection of CXCR4 protein expression in resected tumors. Intraoperative pleural perfusion chemotherapy, with either cisplatin or cisplatin plus matrine, was given to patients with positive PLC. A group of 30 patients with NSCLC that did not undergo intraoperative PLC were used as a control group. Of the 164 study patients, 41 (25%) patients had positive PLC. Serum SDF-1 concentrations were higher in PLC-positive patients compared with patients negative for PLC and control patients. Serum SDF-1 concentrations were also lower at postoperative day 7 in patients treated with cisplatin plus matrine compared with control patients and those perfused with cisplatin alone. A lower incidence of chemotherapy-related adverse events was observed in patients treated with cisplatin plus matrine versus those treated with cisplatin alone during the first postoperative month. Patients with positive PLC showed a higher CXCR4 protein expression than patients with negative PLC. Based on the results of this study, PLC combined with serum SDF-1 concentration measurements may be considered as an effective index to determine the risk of subclinical pleural metastasis in patients with lung cancer. In addition, cisplatin plus matrine was confirmed as an initial approach for pleural perfusion and was superior to cisplatin alone.
Medical Oncology 02/2011; 29(2):574-81. · 2.14 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The first goal of this study was to determine the effect of vascular endothelial growth factor (VEGF) on permeability of the blood-tumor barrier (BTB). The second goal was to determine possible cellular mechanisms by which VEGF increases permeability of the BTB. In the rat C6 glioma model, the permeability of the BTB was significantly increased after VEGF injection at dose of 0.05 ng/g and reached its peak at 45 min. Meanwhile, we observed that the density of pinocytotic vesicles of brain microvascular endothelial cells (BMECs) in the BTB increased dramatically by transmission electron microscopy. The immunohistochemistry and western blot analysis revealed that the expression level of caveolae structure proteins caveolin-1 and caveolin-2 in BMECs was increased after VEGF injection, peaked at 45 min, and then decreased to the untreated level. The time peak of expression level of caveolin-1 and caveolin-2 was identical with the peak time of permeability of the BTB and the density of pinocytotic vesicles. All of these results strongly indicated that VEGF increased permeability of the BTB caused by enhancement of the density of pinocytotic vesicles, and the molecular mechanism might be associated with upregulated expression of caveolin-1 and caveolin-2.
Journal of Molecular Neuroscience 12/2010; 44(2):122-9. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intra-arterial administration of papaverine has been revealed to cause an increase in the blood-brain tumor barrier (BTB) permeability. The exact mechanism of papaverine opening the BTB in chemotherapy of malignant cerebral tumors, however, has not been well described. We used a rat brain glioma (C6) model for studying how papaverine modulates the permeability of BTB by monitoring the activities of the tight junction (TJ)-associated protein occludin, claudin-5 and cytoskeletal protein filamentous actin (F-actin) and whether protein kinase A (PKA) and heat shock protein 70 (HSP70) were involved in the regulation of this biological process. The levels of occludin, claudin-5 and F-actin protein in the tumor tissues were down-regulated by papaverine via immunohistochemistry, immunofluorescence assays and Western blot, corresponding to the time-dependent change of the BTB permeability. The most obvious attenuation of occludin, claudin-5 and F-actin protein was observed at 1h after papaverine perfusion, companied by a significant decrease in expression levels of PKA protein. The expression level of HSP70 in the tumor tissues was also progressively increased after papaverine perfusion and reached the maximum at 3h. The results demonstrate that the reversible openning of BTB mediated by papaverine may be associated with the functional combination between PKA and HSP70. That is, BTB opening may be attributable to the down-regulation of occludin, claudin-5 and F-actin, and cAMP/PKA signaling pathway might be involved in this process. HSP70 is likely responsible for the BTB closing, which helping the repairment of injured TJ protein and the rebuilding of the BTB.
Brain research bulletin 11/2010; 83(6):367-73. · 2.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was performed to determine whether the α subunit of ATP synthase (α-ATP synthase) on brain microvascular endothelial cells (BMECs) serves as the functional target for endothelial monocyte-activating polypeptide-II (EMAP-II)-induced increase in blood-tumor barrier (BTB) permeability. Using a rat C6 glioma model, we found that low-dose (80 ng/kg) EMAP-II significantly decreased the mRNA and protein expression levels of tight junction (TJ)-related proteins claudin-5, occludin, and ZO-1 on BMECs. Meantime, radioimmunity and Western blot assay showed a significant decrease in the expression levels of cAMP and catalytic subunit of protein kinase A (PKAcs) of tumor tissues. Also, pretreatment with specific α-ATP synthase antibody significantly blocked the effects of EMAP-II on TJ-related proteins, cAMP, and PKAcs. In addition, double immunofluorescence assay identified that EMAP-II was co-localized with α-ATP synthase on BMECs. This in vivo study demonstrated that α subunit of ATP synthase on BMECs serves as the functional target for EMAP-II selective opening of the BTB, and that cAMP/PKA signaling transduction pathway might be involved in the modulating process.
Journal of the neurological sciences 10/2010; 300(1-2):52-8. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate whether estrogen modulates learning and memory and long-term potentiation (LTP) in the hippocampus of rats with Alzheimer's disease (AD).
The rats were divided into ovariectomy (OVX) and estrogen replacement therapy (ERT) groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 microL (10 microg/microL) amyloid-beta peptide 1-40(Abeta1-40) into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively.
The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group (P< 0.05). Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation (HFS), compared with that in OVX group (P< 0.01).
ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.
Neuroscience Bulletin 04/2010; 26(2):133-9. · 1.31 Impact Factor
