Anti-apoptotic actions of vasopressin in H32 neurons involve map kinase transactivation and bad phosphorylation
Anti-apoptotic actions of vasopressin in H32 neurons involve map kinase transactivation and bad phosphorylation
复制标题
DOI：
10.1016/j.expneurol.2008.02.023
复制
发表时间：
2008-06-01
影响因子：
5.3
通讯作者：
Aguilera, Greti
中科院分区：
文献类型：
--
作者：
Chen, Jun;Volpi, Simona;Aguilera, Greti
脑内分泌的血管加压素（VP）作为神经递质调节神经元功能。基于观察，VP防止血清剥夺诱导的细胞死亡的神经元细胞系，H32，表达内源性VI受体，我们测试的假设，VP具有抗凋亡特性。流式细胞术实验表明，10 nM VP防止血清剥夺诱导的细胞死亡和膜联蛋白V结合。血清剥夺以时间和血清浓度依赖性方式增加caspase-3活性，VP通过与VI亚型受体相互作用阻止这些作用。VP抗凋亡的信号通路涉及丝裂原活化蛋白激酶（MAP）、细胞外信号调节激酶（ERK）、钙/钙调蛋白依赖性激酶（CaMK）和蛋白激酶C（PKC）。蛋白质印迹分析显示，时间依赖性的减少坏磷酸化和细胞色素c的细胞溶质水平的血清剥夺后，防止10 nM VP的影响。这些数据表明，内源性V1 VP受体的激活通过促凋亡蛋白Bad的磷酸化失活以及随后细胞溶质细胞色素c和半胱天冬酶-3激活的降低来防止血清剥夺诱导的细胞凋亡。这些数据表明，VP在神经元中具有抗凋亡活性，VP可能在脑中起神经保护剂的作用。爱思唯尔公司出版
Vasopressin (VP) secreted within the brain modulates neuronal function acting as a neurotransmitter. Based on the observation that VP prevented serum deprivation-induced cell death in the neuronal cell line, H32, which expresses endogenous VI receptors, we tested the hypothesis that VP has anti-apoptotic properties. Flow cytometry experiments showed that 10 nM VP prevented serum deprivation-induced cell death and annexin V binding. Serum deprivation increased caspase-3 activity in a time and serum concentration dependent manner, and VP prevented these effects through interaction with receptors of VI subtype. The signaling pathways mediating the anti-apoptotic effect of VP involve mitogen activated protein (MAP) kinase and extracellular signal-regulated kinases (ERK), Ca2+/calmodulin dependent kinase (CaMK) and protein kinase C (PKC). Western blot analyses revealed time-dependent decreases of Bad phosphorylation and increases in cytosolic levels of cytochrome c following serum deprivation, effects which were prevented by 10 nM VP. These data demonstrate that activation of endogenous V1 VP receptors prevents serum deprivation-induced apoptosis, through phosphorylation-inactivation of the pro-apoptotic protein, Bad, and consequent decreases in cytosolic cytochrome c and caspase-3 activation. The data suggest that VP has anti-apoptotic activity in neurons and that VP may act as a neuroprotective agent in the brain. Published by Elsevier Inc.