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Crucial role of TRPC6 in maintaining the stability of HIF-1 alpha in glioma cells under hypoxia
文献类型：期刊论文
| 作者 | Li, SS; Wang, JK; Wei, Y; Liu, YJ; Ding, X; Dong, B; Xu, YH; Wang, YZ |
| 刊名 | JOURNAL OF CELL SCIENCE
 |
| 出版日期 | 2015 |
| 卷号 | 128期号:17页码:3317-3329 |
| 关键词 | SMOOTH-MUSCLE-CELLS OPERATED CA2+ CHANNELS CALCIUM OSCILLATIONS CANCER METABOLISM TUMOR-SUPPRESSOR INDUCIBLE FACTOR-1-ALPHA PROLYL HYDROXYLATION ENDOTHELIAL-CELLS DENDRITIC GROWTH CATION CHANNELS |
| 通讯作者 | Wang, YZ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Lab Neural Signal Transduct, Inst Neurosci,State Key Lab Neurosci, Shanghai 200031, Peoples R China.,stocktondb@163.com ; xuyh_dl@126.com ; yzwang@ion.ac.cn |
| 英文摘要 | Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor responsible for the expression of a broad range of genes that facilitate acclimatization to hypoxia. Its stability is predominantly controlled by rapid hydroxylation of two proline residues in its alpha-subunit. However, how the rapid hydroxylation of HIF-1 alpha is regulated is not fully understood. Here, we report that transient receptor potential canonical (TRPC) 6 channels control hydroxylation and stability of HIF-1 alpha in human glioma cells under hypoxia. TRPC6 was rapidly activated by IGF-1R-PLC gamma-IP3R pathway upon hypoxia. Inhibition of TRPC6 enhanced the levels of a-ketoglutarate and promoted hydroxylation of HIF-1 alpha to suppress HIF-1 alpha accumulation without affecting its transcription or translation. Dimethyloxalylglycine N-(methoxyoxoacetyl)-glycine methyl ester (DMOG), an analog of alpha-ketoglutarate, reversed the inhibition of HIF-1 alpha accumulation. Moreover, TRPC6 regulated GLUT1 (also known as SLC2A1) expression in a manner that was dependent on HIF-1 alpha accumulation to affect glucose uptake during hypoxia. Our results suggest that TRPC6 regulates metabolism to affect HIF-1 alpha stability and consequent glucose metabolism in human glioma cells under hypoxia. |
| WOS标题词 | Cell Biology |
| 学科主题 | Cell Biology |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000360715800014 |
| 公开日期 | 2016-02-26 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/3933]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Li, SS,Wang, JK,Wei, Y,et al. Crucial role of TRPC6 in maintaining the stability of HIF-1 alpha in glioma cells under hypoxia[J]. JOURNAL OF CELL SCIENCE,2015,128(17):3317-3329. |
| APA | Li, SS.,Wang, JK.,Wei, Y.,Liu, YJ.,Ding, X.,...&Wang, YZ.(2015).Crucial role of TRPC6 in maintaining the stability of HIF-1 alpha in glioma cells under hypoxia.JOURNAL OF CELL SCIENCE,128(17),3317-3329. |
| MLA | Li, SS,et al."Crucial role of TRPC6 in maintaining the stability of HIF-1 alpha in glioma cells under hypoxia".JOURNAL OF CELL SCIENCE 128.17(2015):3317-3329. |
入库方式： OAI收割
来源：上海神经科学研究所
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