Department of Pathophysiology, Capital Medical University, Beijing 100069, China.
Exp Cell Res. 2010 Jul 1;316(11):1773-83. doi: 10.1016/j.yexcr.2010.02.005. Epub 2010 Feb 10.
The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca(2+) accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.
脂联素及其 G 蛋白偶联受体 APJ 最初从牛胃中分离出来，已在大脑和心血管系统中检测到。最近的研究表明，脂联素可以保护心肌细胞免受缺血损伤。在这里，我们研究了脂联素对培养的小鼠皮质神经元细胞凋亡的影响。将皮质培养物置于无血清培养基中 24 小时诱导核片段化和凋亡死亡；脂联素-13（1.0-5.0 nM）显著阻止了神经元凋亡。脂联素的神经保护作用是通过多种机制介导的。脂联素-13 减少了血清剥夺（SD）诱导的 ROS 生成、线粒体去极化、细胞色素 c 释放和 caspase-3 的激活。脂联素-13 防止了 SD 诱导的 Akt 和 ERK1/2 磷酸化状态的变化。此外，脂联素-13 减轻了 NMDA 诱导的细胞内 Ca2+积累。这些结果表明，脂联素是一种内源性的神经保护脂肪细胞因子，可能通过细胞和分子机制阻断细胞凋亡和兴奋性细胞死亡。提示可以进一步探索脂联素作为缺血性脑损伤的潜在神经保护试剂。
