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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
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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
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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
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ABSTRACT: The strategy for the development of effective and safe neuroprotective agents has great potential to reduce cerebral ischemia-reperfusion injury and improve the functional outcome in stroke patients. Recently, doxycycline, a tetracycline antibiotic, has been shown to have neuroprotective efficiency in reduction of a variety of ischemia-reperfusion injuries as well as ischemic brain damage. We used the rat models of middle cerebral artery occlusion (MCAO) and reperfusion to investigate the effects of treatments with doxycycline against the blood-brain barrier (BBB) leakage at 3, 12, 72, and 120 h of reperfusion. Male Sprague-Dawley rats were subjected to MCAO for 2 h followed by reperfusion for 3, 12, 72, and 120 h and received either doxycycline (45 mg/kg) or saline. The results showed that the treatment of doxycycline significantly reduced the BBB leakage and cerebral infarct volume, which were proved by Evans blue assay and TTC staining. Real-time PCR, immunohistochemistry, and western blot assay verified that the administration of doxycycline significantly up-regulated the expression of tight junction claudin-5, occludin, and ZO-1 from 3 to 120 h after reperfusion. The results of real-time PCR, western blot, and gelatin zymography analyses revealed that the gene and protein expression and activities of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 were significantly elevated in a different time-dependent manner after ischemia-reperfusion but significantly inhibited by doxycycline treatment. Moreover, doxycycline could also significantly down-regulate the expression of PKCδ mRNA and protein after ischemia-reperfusion. These results suggested that the protective effects of doxycycline against BBB damage induced by reperfusion might be related to the up-regulation of tight junction proteins and inhibition of MMP-2, MMP-9, and PKCδ.
Journal of Molecular Neuroscience 12/2011; 47(1):89-100. · 2.50 Impact Factor
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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
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Journal of Molecular Neuroscience 11/2011; · 2.50 Impact Factor
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ABSTRACT: The aberrantly activated antiapoptotic phospatidyl-3-inositol-kinase (PI3K)/Akt signaling induced by cisplatin limits the effectiveness of chemotherapy; inhibition of this pathway may augment the sensitivity of tumor cells to cisplatin-induced toxicity and promote apoptosis. Cross-reacting material 197 (CRM197), the nontoxic mutant of diphtheria toxin, could act as an heparin-binding epidermal growth factor inhibitor and has been shown to have some anticancer effects, but the effect of CRM197 on glioma cells remains unclear. The aim of this study was to investigate the effects of a combination of cisplatin with CRM197 on the growth and apoptosis of human U251 glioma cells and the possible mechanism. In this study, we demonstrated that cisplatin or CRM197 induced a dose-dependent growth inhibition in U251 cells, but cisplatin at 5 µg/ml and CRM197 at 1 µg/ml did not affect the viability of human astrocytes. Cisplatin induced a time-dependent growth inhibition in U251 cells, whereas the growth-inhibitory effects induced by CRM197 alone or combined with cisplatin reached a peak at 24 h after treatment. Compared with the administration of cisplatin or CRM197 alone, CRM197 combined with cisplatin significantly enhanced U251 cell growth inhibition and apoptosis. Cisplatin induced sustained activation of Akt, whereas CRM197 markedly suppressed the Akt phosphorylation induced by cisplatin. The effects of growth inhibition and apoptosis were markedly enhanced after a combination of cisplatin with CRM197 plus the PI3K inhibitor LY294002 or wortmannin. Therefore, CRM197 combined with cisplatin could enhance growth inhibition and apoptosis of glioma cells by inhibiting the cisplatin-induced PI3K/Akt pathway.
Anti-cancer drugs 09/2011; 23(1):81-9. · 2.23 Impact Factor
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ABSTRACT: We have previously shown that activation of RhoA by bradykinin (BK) is associated with cytoskeleton rearrangement, tight junction (TJ) protein disassembly, and an increase in blood-tumor barrier (BTB) permeability in rat brain microvascular endothelial cells (RBMECs). Subsequently, we investigated whether Rho-kinases (ROCKs), a family of downstream effectors of activated RhoA known to stimulate F-actin rearrangement, play a key role in the above-mentioned processes in RBMECs. Our study uses primary RBMECs as an in vitro BTB model and a specific ROCK inhibitor (Y-27632) and ROCK II small interfering RNA (siRNA) to establish whether ROCK plays a role in the process of TJ opening by BK. Y-27632 and ROCK II siRNA could partially inhibit endothelial leakage and restored normal transendothelial electric resistance (TEER) values in RBMECs. A shift in occludin and claudin-5 distribution from insoluble to soluble fractions was prevented by Y-27632. Additionally, Y-27632 inhibited BK-induced relocation of occludin and claudin-5 from cellular borders into the cytoplasm as well as stress fiber formation in RBMECs. A time-dependent increase in phosphorylated myosin light chain (p-MLC) and phosphorylated cofilin (p-cofilin) by BK was observed, which was also inhibited by Y-27632. An increase in ROCK activity by BK was inhibited by Y-27632. ROCK's contribution to BK-induced stress fiber formation is associated with TJ disassembly and an increase in BTB permeability.
Journal of Neuro-Oncology 09/2011; 106(2):291-301. · 3.21 Impact Factor
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ABSTRACT: This study was performed to determine whether recombinant human angiopoietin-1 (Ang-1) decreases the permeability of the blood-brain barrier (BBB) in focal cerebral ischemia and reperfusion rats, whether Ang-1 opens the BBB by affecting tight junction associated proteins zonula occluden-1 (ZO-1), occludin and adherens junction protein vascular endothelial (VE)-cadherin, and whether the protein kinase C (PKC)α/myosin light chain (MLC) signaling pathway involves in it. The rats were divided into eight groups randomly: (1) sham-operated group, (2) ischemia group, (3-5) ischemia-reperfusion (middle cerebral artery occlusion and reperfusion (MCAO/R) 12 h, 48 h, and 7 days) and 0.9% saline groups, (6-8) ischemia-reperfusion (MCAO/R 12 h, 48 h, and 7 days) and Ang-1 groups. The BBB permeability was assessed by Evans blue extravasation. The messenger RNA and protein expressions of ZO-1, occludin, and VE-cadherin were determined by reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry assays. The BBB permeability was significantly decreased after Ang-1 injection. The expressions of ZO-1, occludin, and VE-cadherin were increased after Ang-1 injection. These were in accordance with the results of immunohistochemistry assays. PKCα and phosphorylated MLC (p-MLC) expressions were decreased after Ang-1 injection. This study demonstrated that Ang-1 may decrease the permeability of BBB in MCAO/R rat by upregulation of ZO-1, occludin, and VE-cadherin. The decreased expressions of PKCα and p-MLC induced by Ang-1 also involved in this process.
Journal of Molecular Neuroscience 06/2011; 46(1):236-47. · 2.50 Impact Factor
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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
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ABSTRACT: The clinical chemotherapy of brain tumors has been limited by the blood-tumor barrier (BTB). Low-frequency ultrasound (LFU) in combination with microbubbles might be a useful method for local drug delivery. However, the underlying mechanism remains unclear. In this study, we asked whether LFU changed the permeability of BTB by regulating the tight junction-related proteins. The permeability of BTB was evaluated by Evans blue dye, and the protein and mRNA expression levels of tight junction-related proteins claudin-5, occludin, and ZO-1 were determined by immunohistochemical staining, RT-PCR, and western blot assays. We found that the permeability of BTB increased significantly after LFU exposure in the presence of Optison. The mRNA and protein expression levels of claudin-5, occludin, and ZO-1 decreased significantly at 3 h, restored gradually and nearly recovered after 12 h. The correlation between the increase of BTB permeability and the reduction of tight junction-related proteins suggests that LFU combined with microbubbles may be involved in the opening of the BTB by the tight junction-related proteins.
Journal of Molecular Neuroscience 03/2011; 43(3):364-9. · 2.50 Impact Factor
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ABSTRACT: The research was conducted to study the increase of blood-tumor barrier (BTB) permeability through paracellular pathway by low-frequency ultrasound (LFU) irradiation in vitro. LFU (frequency=1.0 MHz) was performed to irradiate BTB model from the co-culture of rat C6 glioma cells and rat brain microvascular endothelial cells (RBMECs). The permeability of BTB was measured by transendothelial electrical resistance (TEER) and flux of horseradish peroxidase (HRP) assays after LFU irradiation. Western-blotting, immunohistochemistry, and immunofluorescence assays were used to investigate the changes of expressions and distributions of tight junction (TJ)-associated proteins ZO-1, occludin, and claudin-5. The TEER value began to decrease, and the minimum value appeared at 2 h, then gradually returned to the original level at 24 h after LFU irradiation. With time, flux of HRP gradually increased and reached the peak 2 h after LFU irradiation. The expressions of ZO-1, occludin, and claudin-5 in RBMECs decreased, and decreased most significantly at 2 h, then gradually restored to the original level at 24 h. Meanwhile, they were discontinuously distributed in the cellular boundaries after LFU irradiation. In summary, the expression of TJ-associated proteins was down-regulated, TJ was opened, and the permeability of BTB was increased through paracellular pathway by LFU irradiation.
Journal of Molecular Neuroscience 03/2011; 43(3):541-8. · 2.50 Impact Factor
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ABSTRACT: Blood-brain barrier (BBB) leakage plays a key role in cerebral ischemia-reperfusion injury. It is quite necessary to further explore the characteristic and mechanism of BBB leakage during stroke. We induced a focal cerebral ischemia model by transient middle cerebral artery occlusion in male rats for defining the time course of BBB permeability within 120 h following reperfusion and evaluate the specific role of tight junction (TJ) associated proteins claudin-5, occludin, and ZO-1 as well as protein kinase C delta (PKCδ) pathway in BBB leakage induced by reperfusion injury. We verified a bimodal increase in the permeability of the BBB following focal ischemia by Evans blue assay. Two peaks of BBB permeability appeared at 3 h and 72 h of reperfusion after 2 h focal ischemia, respectively. The leak at the endothelial cell was represented at the level of transmission electron microscopy. TTC staining results showed increased infarct size with time after cerebral ischemia reperfusion. The mRNA and protein expression levels of these three TJ associated proteins were significantly decreased compared with the sham-operated group within 120 h of reperfusion, corresponding to the time-dependent change of the biphasic pattern in BBB leakage. The redistribution of claudin-5, occludin, and ZO-1 in ischemia brain microvascular endothelial cells was observed at the same time points. In addition, Western blot assay revealed PKCδ level was also significantly increased in a similar biphasic pattern to above results within 120 h after cerebral ischemia-reperfusion. This study demonstrates the timing of TJ associated proteins claudin-5, occludin, and ZO-1 in light of BBB permeability associated with cerebral ischemia reperfusion, and suggests PKCδ pathway may participate in TJ barrier open and BBB leakage during reperfusion injury in a time-dependent manner.
Journal of Molecular Neuroscience 02/2011; 44(2):130-9. · 2.50 Impact Factor
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ABSTRACT: Cross-reacting material 197 (CRM197), a non-toxin mutant of diphtheria toxin, could act as a diphtheria toxin receptor-specific carrier protein for the targeted delivery of macromolecular substances across the blood-brain barrier (BBB) in vitro. This study was performed to investigate the effects and mechanisms of CRM197 on the permeability of BBB in guinea pigs. Data from the Evans blue extravasation showed that the BBB permeability significantly increased after CRM197 injection in a dose-dependent manner. Transmission electron microscopy indicated CRM197 could induce increased pinocytotic vesicles and vacuoles in brain microvascular endothelial cells. Immunohistochemistry and western blot assay revealed that CRM197 enhanced caveolin-1 protein expression in brain microvessels. The caveolin-1 protein in the membrane fraction of microvessels began to upregulate at 5 min and reached the peak at 10 min after CRM197 treatment, associated by diminished expression of several tight junction-associated proteins ZO-1, occludin, and claudin-5. Thus, our results indicate that the in vivo targeting CRM197 leads to increased BBB permeability via upregulation of caveolin-1 protein, increased pinocytotic vesicles, and redistribution of tight junction-associated proteins in brain microvessels. CRM197 may have a potential application for targeted drug delivery across the BBB.
Journal of Molecular Neuroscience 11/2010; 43(3):485-92. · 2.50 Impact Factor
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ABSTRACT: Blood-brain barrier (BBB) is specialized to limit brain drug delivery. Cross-reacting material 197 (CRM197), a non-toxic mutant of diphtheria toxin, could act as a diphtheria toxin receptor-specific carrier protein and deliver drugs across the BBB. CRM197 has previously been shown to inhibit phospatidyl-3-inositol-kinase (PI3K)/Akt signaling. Other studies have demonstrated a link between PI3K/Akt signaling and forkhead transcription factors in endothelial cells. We therefore investigated the effects and mechanisms underlying the potential of CRM197, not only as a carrier protein for targeted drug delivery to the brain, but also for inducing signaling to affect endocytosis in endothelial cells. The hCMEC/D3 cell line had been used to establish a BBB in vitro model; the transport efficiency of CRM197 was analyzed both by association and transcytosis experiments. CRM197 was shown to prefer apical-to-basal transcytosis, which involved the caveolae-mediated pathway. The uptake of CRM197 conjugates by endothelial cells reached equilibrium after 60 min of treatment. The caveolin-1 mRNA and protein expression levels were significantly increased by CRM197. The up-regulation of caveolin-1 may be mediated by CRM197 via a PI3K/Akt dependent pathway and reduction of the phospho-FOXO1A (forkhead box O) transcription factor. Our results indicate that carrier protein CRM197-mediated delivery across the BBB is involved in the induction of FOXO1A transcriptional activity and upregulation of caveolin-1 expression.
Cellular and Molecular Neurobiology 07/2010; 30(5):717-25. · 1.97 Impact Factor
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ABSTRACT: The research was conducted to study the characteristics of the noninvasive, reversible, targeted opening of the blood-brain barrier (BBB) by use of low-frequency ultrasound (LFU) irradiation and the selective opening of the blood-tumor barrier (BTB) by intracarotid infusion of bradykinin (BK) in small-dose, with the objective of exploring maximum opening of the BTB by combining LFU irradiation with BK infusion. Thus, it provides new therapeutic strategies for targeted transport of macromolecular or granular drugs to the brain. By using the rat C6 glioma model it was shown that extravasation of Evans blue (EB) through the BTB was significantly increased by combining LFU irradiation (frequency = 1.0 MHz, power = 12 mW, duration = 20 s) with intracarotid small-dose BK infusion, compared with utilizing the two methods separately. By transmission electron microscopy (TEM) we observed that this combination significantly increased the number of pinocytotic vesicles of brain microvascular endothelial cells (BMECs) in the BTB. An even more significant increase was observed by using RT-PCR, western blot, immunohistochemistry, and immunofluorescence to detect mRNA and changes of expression of the caveolae structure proteins caveolin-1 and caveolin-2 of BMECs. In summary, this research concludes that LFU irradiation and small-dose BK together selectively enhance the permeability of the BTB and increase the number of pinocytic vesicles of BMECs to a maximum. Significant up-regulation of the level of expression of caveolae structure proteins caveolin-1 and caveolin-2 might be the molecular mechanism of the co-enhanced endocytotic transport by BMECs. Thus, this research provides new therapeutic strategies for targeted transport of macromolecular drugs and the design of drugs.
Journal of Neuro-Oncology 03/2009; 94(1):41-50. · 3.21 Impact Factor
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ABSTRACT: This study was performed to determine whether dexamethasone (DEX) had an effect on calcium-activated potassium channels (KCa channels) in blood-brain tumor barrier (BTB). Using a rat brain glioma model, we found that the expression of KCa channels protein was significantly increased in brain tumor tissue. And bradykinin-induced increase of KCa channels protein was further enhanced after DEX pretreatment for 3 days. In addition, DEX pretreatment enhanced bradykinin-mediated up-regulation of the density of IKCa in the rat brain C6 cells in vitro BTB. Bradykinin markedly increased BTB permeability independent of DEX pretreatment. All of these results strongly suggest that DEX could regulate the target in the transcellular pathway of BTB-KCa channels.
Brain research 02/2009; · 2.46 Impact Factor
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ABSTRACT: Aluminum and zinc are two important trace elements in an organism. Although several studies have demonstrated their impacts on the intelligence, very little was known about their effects on the integrity of blood-brain barrier (BBB). To study the effects of aluminum and zinc on the permeability of BBB, different doses of aluminum and appropriate zinc were administered to rats. Evans blue was detected in brain to determine the permeability of BBB. The ultrastructure of BBB was observed under the transmission electron microscope. Immunohistochemistry and Western blot method were used to detect the expression of skeleton protein F-actin and tight junction protein occludin in brain capillary endothelium. The data indicated that compared with the control group, Evans blue in brains increased (P < 0.01), the ultrastructure of BBB changed and the expression of F-actin and occludin decreased (P < 0.01) in the aluminum-toxic group. Compared with the aluminum-toxic groups, the permeability of BBB to Evans blue decreased (P < 0.01), the damage of the BBB ultrastructure was attenuated and the expression of F-actin and occludin increased (P < 0.05) in the aluminum-zinc group. Our present studies suggest that aluminum increases the permeability of BBB by changing its ultrastructure and the expression of occludin and F-actin. Zinc can protect the integrity of BBB in juvenile rats that are exposed to aluminum and inhibit the decrease of tight junction protein occludin and F-actin expression in BBB.
Neuroscience Letters 09/2008; 445(1):42-6. · 2.11 Impact Factor
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ABSTRACT: In clinical practice there is a difference in response of the blood-tumour barrier (BTB) permeability induced by bradykinin in brain tumours with the same pathology. The variability in response of tumours to bradykinin is likely to be related to the expression level of bradykinin B(2) receptor. This study used fresh human glioma samples to determine the expression level of bradykinin B(2) receptor on gliomas with different pathological grades. The grade of tumour was classified using the WHO classification. To determine the bradykinin B(2) receptor expression level in gliomas, Immunohistochemistry and Western blot methods were used. In 24 cases of gliomas there were eight cases of WHO I glioma, eight cases of WHO II glioma and eight cases of WHO III glioma. Both Western blot and immunohistochemistry showed bradykinin B(2) receptors localized on tumour cells, whilst brain cells at the edge of the glioma hardly expressed B(2) receptor. There were significant differences of bradykinin B(2) receptor expression level among different pathological grades of glioma. The expression of B(2) receptor in the three grades of glioma was in the order of WHO I < WHO II < WHO III. Determination of bradykinin B(2) receptor expression level in human glioma may be useful in screening glioma patients to predict whether they will be suitable for opening of the blood - tumour barrier with bradykinin or its analogue.
British Journal of Neurosurgery 08/2005; 19(4):322-6. · 0.88 Impact Factor
