Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation
Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation
复制标题
DOI：
10.1111/j.1471-4159.2007.04582.x
复制
发表时间：
2007-08-01
影响因子：
4.7
通讯作者：
Santoni, G.
中科院分区：
文献类型：
--
作者：
Amantini, C.;Mosca, M.;Santoni, G.
我们提供的证据表明，瞬时受体电位香草素1型（TRPV 1）的表达胶质瘤细胞，其参与辣椒素（CPS）诱导的细胞凋亡。RT-PCR检测结果显示，与正常人脑星形胶质细胞相比，U373细胞TRPV 1 mRNA的表达量较高，而U87、FC 1和FLS细胞TRPV 1 mRNA的表达量较低。通过流式细胞术，我们发现相当大一部分正常人星形胶质细胞和U87和U373胶质瘤细胞表达TRPV 1蛋白。同时，我们从mRNA和蛋白水平分析了TRPV 1在不同级别胶质瘤组织中的表达。我们发现TRPV 1基因和蛋白表达与胶质瘤分级呈负相关，在大多数IV级多形性胶质母细胞瘤中TRPV 1表达明显缺失。我们还描述了CPS触发U373细胞凋亡，而不是U87细胞。CPS诱导的细胞凋亡涉及Ca ~（2+）内流、p38而非细胞外信号调节的丝裂原活化蛋白激酶激活、磷脂酰丝氨酸暴露、线粒体通透性跨膜孔开放和线粒体跨膜电位耗散、半胱天冬酶3激活和寡核小体DNA片段化。TRPV 1在功能上与这些事件有关，因为它们被TRPV 1拮抗剂辣椒平显著抑制。最后，p38，而不是胞外信号调节蛋白激酶激活所需的TRPV 1介导的CPS诱导的胶质瘤细胞凋亡。
We provide evidence on the expression of the transient receptor potential vanilloid type-1 (TRPV1) by glioma cells, and its involvement in capsaicin (CPS)-induced apoptosis. TRPV1 mRNA was identified by quantitative RT-PCR in U373, U87, FC1 and FLS glioma cells, with U373 cells showing higher, and U87, FC1 and FLS cells lower TRPV1 expression as compared with normal human astrocytes. By flow cytometry we found that a substantial portion of both normal human astrocytes, and U87 and U373 glioma cells express TRPV1 protein. Moreover, we analyzed the expression of TRPV1 at mRNA and protein levels of glioma tissues with different grades. We found that TRPV1 gene and protein expression inversely correlated with glioma grading, with marked loss of TRPV1 expression in the majority of grade IV glioblastorna multiforme. We also described that CPS trigger apoptosis of U373, but not U87 cells. CPS-induced apoptosis involved Ca2+ influx, p38 but not extracellular signal-regulated mitogenactivated protein kinase activation, phosphatidylserine exposure, mitochondrial permeability transmembrane pore opening and mitochondrial transmembrane potential dissipation, caspase 3 activation and oligonucleosomal DNA fragmentation. TRPV1 was functionally implicated in these events as they were markedly inhibited by the TRPV1 antagonist, capsazepine. Finally, p38 but not extracellular signal-regulated protein kinase activation was required for TRPV1-mediated CPS-induced apoptosis of glioma cells.