Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Mol Biol Rep. 2021 May;48(5):4517-4525. doi: 10.1007/s11033-021-06472-0. Epub 2021 Jun 5.
Calcium ions mediate a variety of physiological responses of developing neurons including survival. The purpose of this study was to examine the effect of calcium influx through L-type calcium channels (LTCCs) or NMDA receptors on prostaglandin E (PGE)-induced apoptosis in rat cortical cells. Cultures of rat cortical cells were prepared from an embryonic day 18 rat neocortex. After culturing for 2 or 8 days in vitro (DIV), the cells were subjected to PGE treatment for 48 h. FPL64176, an LTCC agonist, protected the cells at 2 and 8 DIV from PGE-induced apoptosis. On the other hand, N-methyl-D-aspartate (NMDA), an agonist of NMDA receptor, protected the cells from PGE-induced apoptosis only at 8 DIV. FPL64176 increased the calcium levels at 2 and 8 DIV, whereas NMDA increased the calcium levels only at 8 DIV. The protective effects of the LTCC agonist and NMDA on PGE-induced apoptosis were blocked following treatment of the cells with protein kinase C inhibitors. Our results suggest that LTCCs and NMDA receptors modulate the cell death of developing cortical neurons possibly through a protein kinase C pathway.
钙离子介导多种发育神经元的生理反应，包括存活。本研究的目的是研究通过 L 型钙通道 (LTCC) 或 NMDA 受体的钙内流对前列腺素 E (PGE) 诱导的大鼠皮质细胞凋亡的影响。大鼠皮质细胞培养物是从胚胎第 18 天的大鼠新皮层中制备的。体外培养 2 或 8 天后 (DIV) ，用 PGE 处理细胞 48 小时。LTCC 激动剂 FPL64176 可保护 2 和 8 DIV 的细胞免受 PGE 诱导的凋亡。另一方面，NMDA，即 NMDA 受体激动剂，仅在 8 DIV 时保护细胞免受 PGE 诱导的凋亡。FPL64176 增加了 2 和 8 DIV 的钙水平，而 NMDA 仅在 8 DIV 时增加钙水平。LTCC 激动剂和 NMDA 对 PGE 诱导的凋亡的保护作用被细胞蛋白激酶 C 抑制剂处理所阻断。我们的结果表明，LTCC 和 NMDA 受体可能通过蛋白激酶 C 途径调节发育中皮质神经元的细胞死亡。
