Wang Bin, Li Wenjun, Meng Xiaojing, Zou Fei
School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
Neurosci Lett. 2009 Aug 14;459(3):132-6. doi: 10.1016/j.neulet.2009.05.015. Epub 2009 May 13.
Canonical Transient Receptor Potential (TRPC) channels play important roles in diverse physiological processes. The contribution of TRPC channels to up-regulate VEGF expression under hypoxic conditions was studied in a malignant glioma cell line, U-87 MG cells. Up-regulation of VEGF gene expression by hypoxia was markedly suppressed by a TRPC channel blocker. RT-PCR showed that U-87 MG cells expressed four TRPC isoforms in normoxia: TRPC1, 3, 4, and 5. In addition, the expression of TRPC3, 4, and 5 decreased greatly under hypoxia exposure in U-87 MG cells. In contrast, TRPC1 expression was unchanged. These results suggest TRPC channels were involved in hypoxia-induced VEGF expression, and compared with other TRPC isoforms, TRPC1 might play a different role in this process. Furthermore, we determined the function of TRPC1 by RNAi. Two different siRNAs against TRPC1 largely inhibited hypoxia-induced up-regulation of VEGF mRNA and protein levels. However, overexpression of TRPC3 or 5 neither enhanced hypoxia-induced VEGF expression, nor prevented it. Taken together, our present data suggest that TRPC1, but not TRPC3 or 5, is involved in hypoxia-induced VEGF expression in U-87 MG cells.
典型瞬时受体电位（TRPC）通道在多种生理过程中发挥重要作用。在恶性胶质瘤细胞系U - 87 MG细胞中，研究了TRPC通道在缺氧条件下对上调血管内皮生长因子（VEGF）表达的作用。TRPC通道阻滞剂可显著抑制缺氧对VEGF基因表达的上调作用。逆转录聚合酶链反应（RT-PCR）显示，U - 87 MG细胞在常氧条件下表达四种TRPC亚型：TRPC1、3、4和5。此外，在U - 87 MG细胞中，缺氧暴露后TRPC3、4和5的表达大幅下降。相比之下，TRPC1的表达没有变化。这些结果表明TRPC通道参与了缺氧诱导的VEGF表达，并且与其他TRPC亚型相比，TRPC1在这一过程中可能发挥不同的作用。此外，我们通过RNA干扰确定了TRPC1的功能。两种针对TRPC1的不同小干扰RNA（siRNA）在很大程度上抑制了缺氧诱导的VEGF mRNA和蛋白水平的上调。然而，TRPC3或5的过表达既没有增强缺氧诱导的VEGF表达，也没有阻止这种表达。综上所述，我们目前的数据表明，在U - 87 MG细胞中，参与缺氧诱导的VEGF表达的是TRPC1，而不是TRPC3或5。
