Wu Jang-Yen, Wu Heng, Jin Ying, Wei Jianning, Sha Di, Prentice Howard, Lee Hsin-Hsueh, Lin Chun-Hua, Lee Yi-Hsuan, Yang Ling-Ling
Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA.
Adv Exp Med Biol. 2009;643:169-79. doi: 10.1007/978-0-387-75681-3_17.
Taurine has potent protective function against glutamate-induced neuronal injury presumably through its function in regulation of intracellular free calcium level, [Ca2+]i. In this communication, we report that taurine exerts its protective function through one or more of the following mechanisms: 1. Inhibition of glutamate-induced calcium influx through L-, N- and P/Q-type voltage-gated calcium channels and NMDA receptor calcium channel; 2. Attenuation of glutamate-induced membrane depolarization; 3. Prevention of glutamate-induced apoptosis via preventing glutamate-mediated down-regulation of Bcl-2; 4. Prevention of cleavage of Bcl-2 by calpain. This action of taurine is due to its inhibition on glutamate induced calpain activation. Based on these observations, we propose that taurine protects neurons against glutamate-induced neurotoxicity in part, by preventing glutamate-induced membrane depolarization, elevation of [Ca2+]i, activation of calpain, reduction of Bcl-2 and apoptosis.
牛磺酸可能通过调节细胞内游离钙水平[Ca2+]i,对谷氨酸诱导的神经元损伤具有强大的保护作用。在本通讯中,我们报告牛磺酸通过以下一种或多种机制发挥其保护作用:1. 抑制谷氨酸通过L型、N型和P/Q型电压门控钙通道以及NMDA受体钙通道诱导的钙内流;2. 减轻谷氨酸诱导的膜去极化;3. 通过防止谷氨酸介导的Bcl-2下调来预防谷氨酸诱导的细胞凋亡;4. 防止钙蛋白酶切割Bcl-2。牛磺酸的这种作用是由于其抑制了谷氨酸诱导的钙蛋白酶激活。基于这些观察结果,我们提出牛磺酸部分地通过防止谷氨酸诱导的膜去极化、[Ca2+]i升高、钙蛋白酶激活、Bcl-2减少和细胞凋亡来保护神经元免受谷氨酸诱导的神经毒性。