Semenov Dmitry G, Belyakov Alexandr V, Glushchenko Tatjana S, Samoilov Mikhail O, Salinska Elzbieta, Lazarewicz Jerzy W
Pavlov Institute of Physiology, Russian Academy of Sciences, Nab. Makarova, 6, Saint Petersburg, Russia, 199034.
Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106, Warsaw, Poland.
Neurochem Res. 2015 Nov;40(11):2200-10. doi: 10.1007/s11064-015-1708-9. Epub 2015 Aug 29.
The study assessed involvement of Ca(2+) signaling mediated by the metabotropic glutamate receptors mGluR1/5 in brain tolerance induced by hypoxic preconditioning. Acute slices of rat piriform cortex were tested 1 day after exposure of adult rats to mild hypobaric hypoxia for 2 h at a pressure of 480 hPa once a day for three consecutive days. We detected 44.1 ± 11.6 % suppression of in vitro anoxia-induced increases of intracellular Ca(2+) levels and a fivefold increase in Ca(2+) transients evoked by selective mGluR1/5 agonist, DHPG. Western blot analysis of cortical homogenates demonstrated a 11 ± 4 % decrease in mGluR1 immunoreactivity (IR), and in the nuclei-enriched fraction a 12 ± 3 % increase in IR of phospholipase Cβ1 (PLCβ1), which is a major mediator of mGluR1/5 signaling. Immunocytochemical analysis of the cortex revealed increase in the mGluR1/5 and PLCβ1 IR in perikarya, and a decrease in IR of the neuronal inositol trisphosphate receptors (IP3Rs). We suggest that enhanced expression of mGluR5 and PLCβ1 and potentiation of Ca(2+) signaling may represent pro-survival upregulation of Ca(2+)-dependent genomic processes, while decrease in mGluR1 and IP3R IR may be attributed to a feedback mechanism preventing excessive intracellular Ca(2+) release.
该研究评估了代谢型谷氨酸受体mGluR1/5介导的Ca(2+)信号传导在缺氧预处理诱导的脑耐受性中的作用。成年大鼠连续三天每天在480 hPa压力下暴露于轻度低压缺氧环境2小时，1天后对大鼠梨状皮质急性切片进行测试。我们检测到体外缺氧诱导的细胞内Ca(2+)水平升高受到44.1±11.6%的抑制，并且选择性mGluR1/5激动剂DHPG诱发的Ca(2+)瞬变增加了五倍。对皮质匀浆的蛋白质免疫印迹分析表明，mGluR1免疫反应性（IR）降低了11±4%，在富含细胞核的部分，磷脂酶Cβ1（PLCβ1）的IR增加了12±3%，PLCβ1是mGluR1/5信号传导的主要介质。对皮质的免疫细胞化学分析显示，mGluR1/5和PLCβ1在核周体中的IR增加，而神经元肌醇三磷酸受体（IP3Rs）的IR降低。我们认为，mGluR5和PLCβ1表达增强以及Ca(2+)信号传导增强可能代表了Ca(2+)依赖性基因组过程的促生存上调，而mGluR1和IP3R IR降低可能归因于防止细胞内Ca(2+)过度释放的反馈机制。
