Qin Wang

Publications of Qin Wang

• Monocyte-endothelial adhesion is modulated by Cx43-stimulated ATP release from monocytes.

  Authors: Dongdong Yuan, Qin Wang, Dengpan Wu, Meiling Yu, Suzhi Zhang, Li Li, Liang Tao, Andrew L Harris

  Biochemical and biophysical research communications. 03/2012;

  Adhesion of circulating monocytes to vascular endothelial cells is a crucial event in development of vascular inflammatory conditions, including atherosclerosis. We investigated the roles ofAdhesion of circulating monocytes to vascular endothelial cells is a crucial event in development of vascular inflammatory conditions, including atherosclerosis. We investigated the roles of connexin43 (Cx43) and ATP release on monocyte-endothelial adhesion. Cx43 function and expression were manipulated by connexin channel inhibitors, overexpression and siRNA. Connexin channel inhibitors rapidly decreased ATP release from U937 monocytes and increased adhesion to human umbilical vein endothelial cells (HUVEC). Monocyte ATP release correlated with Cx43 expression, not with Cx37 expression. Exogenous adenosine (ADO) or ATP decreased adhesion, and inhibition of ATP conversion to ADO increased adhesion. We infer that monocyte Cx43 channel activity causes ATP release, likely via Cx43-containing hemichannels, and that ATP decreases adhesion via conversion to ADO. Inhibition of HUVEC connexin channel activity did not affect ATP release or adhesion. In contrast, expression of Cx43 protein in U937 cells enhanced adhesion. Thus, Cx43 channel function and expression have opposite effects: Cx43 channel function in monocytes, but not in HUVEC, rapidly decreases adhesion via ATP release and conversion to ADO, whereas Cx43 expression itself enhances adhesion. These studies suggest that local regulation of monocyte Cx43 activity within the vasculature can dynamically modulate the monocyte-endothelial adhesion that is an initiating event in vascular inflammatory pathologies, with the baseline adhesion set by Cx43 expression levels. This balance of rapid and tonic influences may be crucial in development of vascular pathologies.

• Gap junctions propagate opposite effects in normal and tumor testicular cells in response to cisplatin.

  Authors: Xiaoting Hong, Qin Wang, Yan Yang, Suping Zheng, Xuhui Tong, Suzhi Zhang, Liang Tao, Andrew L Harris

  Cancer letters. 11/2011; 317(2):165-71.

  Gap junctions propagate toxic effects among tumor cells during chemotherapy, but could also enhance killing of normal cells by the same mechanism. We show that the effect of gap junctionalGap junctions propagate toxic effects among tumor cells during chemotherapy, but could also enhance killing of normal cells by the same mechanism. We show that the effect of gap junctional intercellular communication (GJIC) on cisplatin toxicity differs between normal and tumor testicular cells. Downregulation of GJIC by each of several different manipulations (no cell contact, pharmacological inhibition, siRNA suppression) decreased cisplatin cytoxicity in tumor cells but enhanced it in normal cells. Enhanced toxicity due to GJIC downregulation in normal cells correlated with increased DNA interstrand crosslinks. Thus, GJIC protects normal cells from cisplatin toxicity while enhancing it in tumor cells, suggesting that enhancement/maintenance of GJIC increases therapeutic efficacy while decreasing off-target toxicity.

• Connexin 32 and its derived homotypic gap junctional intercellular communication inhibit the migration and invasion of transfected HeLa cells via enhancement of intercellular adhesion.

  Authors: Jie Yang, Bing Liu, Qin Wang, Dongdong Yuan, Xiaoting Hong, Yan Yang, Liang Tao

  Molecular medicine reports. 06/2011; 4(5):971-9.

  The effects of connexin (Cx) and its derived homotypic gap junctional intercellular communication (GJIC) between tumor cells on the invasion of metastatic cancers and the underlying mechanisms remainThe effects of connexin (Cx) and its derived homotypic gap junctional intercellular communication (GJIC) between tumor cells on the invasion of metastatic cancers and the underlying mechanisms remain unclear. In this study, we investigated the influence of Cx32 and the homotypic GJIC mediated by this Cx on the migration, invasion and intercellular adhesion of transfected HeLa cells. The expression of Cx32 significantly increased cell adhesion and inhibited migration and invasion. The inhibition of GJIC by oleamide, a widely used GJIC inhibitor, reduced the enhanced adhesion and partly reversed the decreased migration and invasion that had been induced by Cx32 expression. Blockage of the p38 and extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase (ERK1/2 MAPKs) pathways using their specific inhibitors attenuated the effects of Cx32, but not those of GJIC, on cell adhesion, migration and invasion. These results indicate that the homotypic GJIC mediated by Cx32, as well as the Cx itself, inhibit cell migration and invasion, most likely through the elevation of intercellular adhesion. The suppressive effect of Cx32 on the migration and invasion of cancer cells, but not that of its derived homotypic GJIC, partly depends on the activation of the p38 and the ERK1/2 MAPKs pathways.

• Berberine potentizes apoptosis induced by X-rays irradiation probably through modulation of gap junctions.

  Authors: Bing Liu, Qin Wang, Dong-dong Yuan, Xiao-ting Hong, Liang Tao

  Chinese medical journal. 04/2011; 124(8):1221-8.

  Clinical combination of some traditional Chinese medical herbs, including berberine, with irradiation is demonstrated to improve efficacy of tumor radiotherapy, yet the mechanisms for such effectClinical combination of some traditional Chinese medical herbs, including berberine, with irradiation is demonstrated to improve efficacy of tumor radiotherapy, yet the mechanisms for such effect remain largely unknown. The present study investigated the effect of berberine on apoptosis induced by X-rays irradiation and the relation between this effect and gap junction intercellular communication (GJIC). The role of gap junctions in the modulation of X-rays irradiation-induced apoptosis was explored by manipulation of connexin (Cx) expression, and gap junction function, using oleamide, a GJIC inhibitor, and berberine. In transfected HeLa cells, Cx32 expression increased apoptosis induced by X-rays irradiation, while inhibition of gap junction by oleamide reduced the irradiation responses, indicating the dependence of X-rays irradiation-induced apoptosis on GJIC. Berberine, at the concentrations without cytotoxicity, enhanced apoptosis induced by irradiation only in the presence of functional gap junctions. These results suggest that berberine potentizes cell apoptosis induced by X-rays irradiation, probably through enhancement of gap junction activity.

• Propofol depresses the cytotoxicity of X-ray irradiation through inhibition of gap junctions.

  Authors: Yuping Zhao, Bing Liu, Qin Wang, Dongdong Yuan, Yan Yang, Xiaoting Hong, Xudong Wang, Liang Tao

  Anesthesia and analgesia. 03/2011; 112(5):1088-95.

  General anesthetics (e.g., propofol) influence the therapeutic activity of intraoperative radiotherapy but the mechanism of the effects is largely unknown. It has been reported that propofol inhibitsGeneral anesthetics (e.g., propofol) influence the therapeutic activity of intraoperative radiotherapy but the mechanism of the effects is largely unknown. It has been reported that propofol inhibits gap junction (GJ) function briefly, and a functional GJ enhances the efficacy of radiotherapy in some cancer cells. Yet the mechanisms underlying the inhibition of GJ function by propofol and the influence of propofol on therapeutic activity of intraoperative radiotherapy are unknown. The role of propofol at clinically relevant concentrations in the modulation of radiograph-induced cytotoxicity in HeLa cells transfected with connexin 32 (Cx32) plasmid was explored by manipulation of connexin expression, GJ presence, and function. GJ function, Cx32 protein level, and Cx32 mRNA expression were determined by "Parachute" dye-coupling assay, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively. Propofol significantly reduced radiograph-induced cytotoxicity only in the presence of functional GJ. Four-hour propofol exposure inhibited GJ function mainly by diminution of Cx32 protein levels but without influence on Cx32 mRNA expression. These results suggest that propofol inhibits the function of the GJ through the reduction of Cx32 protein levels by a transcription-independent mechanism. They further indicate that propofol depresses the cytotoxicity of radiograph irradiation through inhibition of GJ activity.

• The effects of 2-aminoethoxydiphenyl borate and diphenylboronic anhydride on gap junctions composed of Connexin43 in TM₄ sertoli cells.

  Authors: Yan Yang, Ming-Hui Cao, Qin Wang, Dong-Dong Yuan, Li Li, Liang Tao

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1390-7.

  2-Aminoethoxydiphenyl borate (2-APB) has recently been demonstrated to inhibit gap junction (GJ) channels, whereas the underlying mechanisms are still unknown. Using mouse TM₄ Sertoli cell which2-Aminoethoxydiphenyl borate (2-APB) has recently been demonstrated to inhibit gap junction (GJ) channels, whereas the underlying mechanisms are still unknown. Using mouse TM₄ Sertoli cell which expresses connexin43 (Cx43), we explored the effects of 2-APB and its analogues on dye-coupling through junctional channels formed by Cx43 and on expression of Cx43. Exposure of the cells to 2-APB (1-50 µM) and one of its analogues diphenylboronic anhydride (DPBA) (1-30 µM) for 4 h leads to a significant decrease in dye coupling of GJ in a concentration-dependent manner. The inhibitory effects of 2-APB and DPBA are reversible since decreased GJ coupling resumes after the two compounds are washed out. The disfunction of GJ induced by 2-APB and DPBA is associated with a decrease in total amount of Cx43 protein and number of GJs on the cell membrane. 2-APB and DPBA do not alter Cx43 phosphorylation state and the level of Cx43 mRNA expression. The loss of Cx43 protein is prevented by either lysosomal or proteasomal inhibitor, suggesting that the decrease in Cx43 results from a 2-APB or DPBA-enhanced degradation of Cx43. The present results indicate that 2-APB and DPBA inhibit GJ communication through decreasing Cx43 expression in TM₄ cells.

• Effects of carvedilol on delayed rectifier and transient inactivating potassium currents in rat hippocampal CA1 neurons.

  Authors: Jing-Jing Duan, Qin Wang, Chun-Yu Deng, Su-Juan Kuang, Ru-Zhu Chen, Liang Tao

  Clinical and experimental pharmacology & physiology. 10/2010; 37(10):996-1003.

  1. The aims of the present study were to investigate the mechanism(s) underlying the protective effect of carvedilol against neural damage. 2. The transient inactivating potassium current (I(A) ) and1. The aims of the present study were to investigate the mechanism(s) underlying the protective effect of carvedilol against neural damage. 2. The transient inactivating potassium current (I(A) ) and the delayed rectifier potassium current (I(K) ) in rat hippocampal CA1 pyramidal neurons were recorded using whole-cell patch-clamp techniques. 3. Carvedilol (0.1-3 μmol/L) significantly inhibited I(K) with an IC(50) of 1.3 μmol/L and the inhibition was voltage independent. Over the same concentration range, carvedilol had no effect on the amplitude of I(A). At 1 μmol/L, carvedilol did not significantly change the steady state activation curves of I(A) and I(K), but did negatively shift their steady state inactivation curves. Recovery from inactivation was slowed for both I(A) and I(K). The inhibitory effect of carvedilol on I(K) was not affected by the adrenoceptor agonists phenylephrine and prazosin or the adrenoceptor antagonist isoproterenol, but propranolol was able to shift the dose-response curve of carvedilol for I(K) to the right. 4. Because I(K) is the main pathway for loss of intracellular potassium from depolarized neurons, selective obstruction of I(K) by carvedilol could be useful for neuroprotection.

• Cisplatin and oxaliplatin inhibit gap junctional communication by direct action and by reduction of connexin expression, thereby counteracting cytotoxic efficacy.

  Authors: Qin Wang, Tianhui You, Dongdong Yuan, Xu Han, Xiaoting Hong, Bo He, Lingzhi Wang, Xuhui Tong, Liang Tao, Andrew L Harris

  The Journal of pharmacology and experimental therapeutics. 03/2010; 333(3):903-11.

  Cisplatin [cis-diamminedichloroplatinum(II)]/oxaliplatin [1,2-diamminocyclohexane(trans-1)oxolatoplatinum(II)] toxicity is enhanced by functional gap junctions between treated cells, implying thatCisplatin [cis-diamminedichloroplatinum(II)]/oxaliplatin [1,2-diamminocyclohexane(trans-1)oxolatoplatinum(II)] toxicity is enhanced by functional gap junctions between treated cells, implying that inhibition of gap junctions may decrease cytotoxic activity of these platinum-based agents. This study investigates the effect of gap junction modulation by cisplatin/oxaliplatin on cytotoxicity in a transformed cell line. The effects were explored using junctional channels expressed in transfected HeLa cells and purified hemichannels. Junctional channels showed a rapid, dose-dependent decrease in dye coupling with exposure to cisplatin/oxaliplatin. With longer exposure, both compounds also decreased connexin expression. Both compounds inhibit the activity of purified connexin hemichannels, over the same concentration range that they inhibit junctional dye permeability, demonstrating that inhibition occurs by direct interaction of the drugs with connexin protein. Cisplatin/oxaliplatin reduced the clonogenic survival of HeLa cells at low density and high density in a dose-dependent manner, but to a greater degree at high density, consistent with a positive effect of gap junctional intercellular communication (GJIC) on cytotoxicity. Reduction of GJIC by genetic or pharmacological means decreased cisplatin/oxaliplatin toxicity. At low cisplatin/oxaliplatin concentrations, where effects on connexin channels are minimal, the toxicity increased with increased cell density. However, higher concentrations strongly inhibited GJIC, and this counteracted the enhancing effect of greater cell density on toxicity. The present results indicate that inhibition of GJIC by cisplatin/oxaliplatin decreases their cytotoxicity. Direct inhibition of GJIC and reduction of connexin expression by cisplatin/oxaliplatin may thereby compromise the effectiveness of these compounds and be a factor in the development of resistance to this class of chemotherapeutic agents.

• Tramadol and Flurbiprofen Depress the Cytotoxicity of Cisplatin via Their Effects on Gap Junctions.

  Authors: Bo He, Xuhui Tong, Lingzhi Wang, Qin Wang, Hua Ye, Bing Liu, Xiaoting Hong, Liang Tao, Andrew L Harris

  Clinical cancer research : an official journal of the American Association for Cancer Research. 10/2009;

  PURPOSE: Cancer patients are often concurrently treated with analgesics and antineoplastic drugs, yet the influence of analgesic agents on therapeutic activity of antineoplastic drugs is largelyPURPOSE: Cancer patients are often concurrently treated with analgesics and antineoplastic drugs, yet the influence of analgesic agents on therapeutic activity of antineoplastic drugs is largely unexplored. This study investigates the effects of three commonly used analgesics, which produce analgesia by different mechanisms, on cytotoxicity induced by cisplatin, a widely used antitumor agent, and the relation between those effects and modulation of gap junction function by the analgesics. EXPERIMENTAL DESIGN: The role of gap junctions in the modulation of cisplatin toxicity is explored by manipulation of connexin expression, and gap junction presence and function, using clinically relevant concentrations of the analgesics and cisplatin. RESULTS: Short-term exposure of transformed cells to cisplatin reduced the clonogenic survival in low-density cultures (without gap junction formation) and in high density (with gap junction formation), but the toxic effect was greater at high density. In the absence of connexin expression or with block of connexin channels, cell density had no effect on cisplatin toxicity. Tramadol and flurbiprofen, but not morphine, significantly reduced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Tramadol and flurbiprofen inhibited dye-coupling through gap junctions, but morphine did not. CONCLUSIONS: The results suggest that the density dependence of cisplatin toxicity is mediated by gap junctions. They further indicate that tramadol and flurbiprofen depress cisplatin cytotoxicity through inhibition of gap junction activity, and more generally, that agents that depress junctional communication can counteract the effects of antitumor agents. (Clin Cancer Res 2009;15(18):OF1-8).