Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/68299
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dc.contributor.authorCheng, C.H.en_US
dc.contributor.author陳鴻震zh_TW
dc.contributor.authorHsieh, C.L.en_US
dc.contributor.authorShu, K.H.en_US
dc.contributor.authorChen, Y.L.en_US
dc.contributor.authorChen, H.C.en_US
dc.date2002zh_TW
dc.date.accessioned2014-06-11T05:56:36Z-
dc.date.available2014-06-11T05:56:36Z-
dc.identifier.issn0014-5793zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/68299-
dc.description.abstractCalcium channel antagonists have been reported to have a favorable impact on cyclosporin A (CsA)-treated kidney transplant recipients. However, it is not clear whether this is because of their direct effect on antagonizing the toxicity of CsA to renal tubular cells. In this study, we have used Madin-Darby canine kidney tubular cells as a model to examine the effect of diltiazem, a calcium channel antagonist, on CsA-induced apoptosis. Moreover, to investigate the possible regulation of CsA cytotoxicity by intracellular calcium level, the effect of the calcium ionophore A23187 on CsA-induced apoptosis was also examined. We found that treatment of CsA (20 muM) alone caused 20-30% cell death, which was apparently (30-40%) enhanced by diltiazem at 100 mug/ml, accompanied by more severe DNA fragmentation. activation of caspases, and a decreased level of Bcl-2. The caspase inhibitor ZVAD-fmk or Bcl-2 overexpression was capable of suppressing apoptosis induced by the synergistic effect of diltiazem and CsA. Moreover, the survival rate of cells treated with CsA (30 muM) alone remained only 30%, however, it was markedly (similar to40%) elevated by cotreatment with A23187 (75 ng/ml). The rescue of cells from CsA-induced apoptosis by A23187 was correlated with AKT activation, BAD phosphorylation, and caspase-3 inactivation. Taken together, our results suggest that the reported favorable impact of diltiazem on kidney grafts is likely not because of its direct protection on renal tubular cells. Instead, it enhances the toxicity of CsA to renal tubular cells. In addition, our findings raise a possibility that the intracellular calcium level and the AKT pathway may participate in the regulation of CsA cytotoxicity. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.en_US
dc.language.isoen_USzh_TW
dc.relationFebs Lettersen_US
dc.relation.ispartofseriesFebs Letters, Volume 516, Issue 1-3, Page(s) 191-196.en_US
dc.relation.urihttp://dx.doi.org/10.1016/s0014-5793(02)02563-2en_US
dc.subjectcyclosporinen_US
dc.subjectapoptosisen_US
dc.subjectdiltiazemen_US
dc.subjectcalcium ionophoreen_US
dc.subjectAKTen_US
dc.subjecthepatocyte growth-factoren_US
dc.subjectfocal adhesion kinaseen_US
dc.subjectsignal-transductionen_US
dc.subjectnf-aten_US
dc.subjectnephrotoxicityen_US
dc.subjectkidneyen_US
dc.subjectphosphorylationen_US
dc.subjectnephropathyen_US
dc.subjectactivationen_US
dc.subjectmechanismsen_US
dc.titleEffect of calcium channel antagonist diltiazem and calcium ionophore A23187 on cyclosporine A-induced apoptosis of renal tubular cellsen_US
dc.typeJournal Articlezh_TW
dc.identifier.doi10.1016/s0014-5793(02)02563-2zh_TW
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