| First Author | Inoue K | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 10 | Pages | 7430-9 |
| PubMed ID | 20048154 | Mgi Jnum | J:165956 |
| Mgi Id | MGI:4838965 | Doi | 10.1074/jbc.M109.040485 |
| Citation | Inoue K, et al. (2010) Zinc-induced neurotoxicity mediated by transient receptor potential melastatin 7 channels. J Biol Chem 285(10):7430-9 |
| abstractText | Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca(2+)-permeable non-selective cation channels ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in cellular Mg(2+) homeostasis, diseases caused by abnormal magnesium absorption, and in Ca(2+)-mediated neuronal injury under ischemic conditions. Here we show strong evidence suggesting that TRPM7 channels also play an important role in cellular Zn(2+) homeostasis and in Zn(2+)-mediated neuronal injury. Using a combination of fluorescent Zn(2+) imaging, small interfering RNA, pharmacological analysis, and cell injury assays, we show that activation of TRPM7 channels augmented Zn(2+)-induced injury of cultured mouse cortical neurons. The Zn(2+)-mediated neurotoxicity was inhibited by nonspecific TRPM7 blockers Gd(3+) or 2-aminoethoxydiphenyl borate, and by knockdown of TRPM7 channels with small interfering RNA. In addition, Zn(2+)-mediated neuronal injury under oxygen-glucose deprivation conditions was also diminished by silencing TRPM7. Furthermore, we show that overexpression of TRPM7 channels in HEK293 cells increased intracellular Zn(2+) accumulation and Zn(2+)-induced cell injury, while silencing TRPM7 by small interfering RNA attenuated the Zn(2+)-mediated cell toxicity. Thus, TRPM7 channels may represent a novel target for neurological disorders where Zn(2+) toxicity plays an important role. |
