Kim Hyungsu, Moon Sunhong, Kim Minsu, Oh Hyungkeun, Park Jinhong, Kim Suji, Yoo Taehyung, Kim Ji-Yoon, Kim Yonghee, Kim Young-Myeong, Choi Yoon Kyung
Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea.
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
J Cereb Blood Flow Metab. 2025 May 2:271678X251332760. doi: 10.1177/0271678X251332760.
Korean red ginseng extract (KRGE) enhances astrocytic functions through hypoxia-inducible factor-1α (HIF-1α). Astrocytic Ca influx through L-type Ca channels (LTCCs) facilitates neurovascular communication, while the large-conductance Ca- and voltage-activated K (BK) channel mediates K efflux for vasodilation. However, the role of LTCC subunits in KRGE-mediated BKα and HIF-1α expression in astrocytes remains unclear. This study aimed to investigate the effects of KRGE on LTCC subunits, cytosolic Ca influx, and BKα and HIF-1α induction in human astrocytes. The levels of BKα, LTCCs, and HIF-1α were analyzed in KRGE-treated mouse brain tissue using immunohistochemistry. Human astrocytes treated with an LTCC agonist exhibited increased BKα and HIF-1α protein levels. Similarly, KRGE increased the levels of LTCC subunits α1 C and β4, cytosolic Ca influx, BKα, and HIF-1α. Moreover, knockdown of either α1 C or β4 attenuated KRGE-induced increases in Ca influx and HIF-1α levels. Notably, their combined knockdown synergistically reduced KRGE-induced increases in BKα levels, mitochondrial mass, ATP production, and O consumption. The corpus callosum astrocytes of KRGE-treated mice exhibited increased levels of α1 C and β4, BKα, HIF-1α, and cAMP-response element binding protein (CREB). Collectively, these findings suggest that KRGE induced astrocytic BKα and HIF-1α expression via LTCC-mediated Ca influx and subsequent CREB activation.
韩国红参提取物（KRGE）通过缺氧诱导因子-1α（HIF-1α）增强星形胶质细胞功能。星形胶质细胞通过L型钙通道（LTCCs）的钙内流促进神经血管通讯，而大电导钙和电压激活钾（BK）通道介导钾外流以实现血管舒张。然而，LTCC亚基在KRGE介导的星形胶质细胞中BKα和HIF-1α表达中的作用仍不清楚。本研究旨在探讨KRGE对人星形胶质细胞中LTCC亚基、胞质钙内流以及BKα和HIF-1α诱导的影响。使用免疫组织化学分析KRGE处理的小鼠脑组织中BKα、LTCCs和HIF-1α的水平。用LTCC激动剂处理的人星形胶质细胞显示BKα和HIF-1α蛋白水平增加。同样，KRGE增加了LTCC亚基α1C和β4、胞质钙内流、BKα和HIF-1α的水平。此外，敲低α1C或β4可减弱KRGE诱导的钙内流和HIF-1α水平的增加。值得注意的是，它们的联合敲低协同降低了KRGE诱导的BKα水平、线粒体质量、ATP产生和氧消耗的增加。KRGE处理的小鼠胼胝体星形胶质细胞中α1C和β4、BKα、HIF-1α和cAMP反应元件结合蛋白（CREB）的水平增加。总的来说，这些发现表明KRGE通过LTCC介导的钙内流和随后的CREB激活诱导星形胶质细胞BKα和HIF-1α表达。
