Hypoxia up-regulates vascular endothelial growth factor in U-87 MG cells: involvement of TRPC1.
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.
Wang
Bin
B
School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
Li
Wenjun
W
Meng
Xiaojing
X
Zou
Fei
F
D002121:Calcium Channel Blockers / Q000008:administration & dosage; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D002121:Calcium Channel Blockers; D007093:Imidazoles; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C489571:TRPC4 ion channel; C491780:TRPC5 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C096351:transient receptor potential cation channel, subfamily C, member 1; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D010100:Oxygen