Epinephrine increases phosphorylation of MAP-2c in rat pheochromocytoma cells (PC12 Cells) via a protein kinase C- and mitogen activated protein kinase-dependent mechanism.
Epinephrine increases phosphorylation of MAP-2c in rat pheochromocytoma cells (PC12 Cells) via a protein kinase C- and mitogen activated protein kinase-dependent mechanism.
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DOI：
10.1021/pr700711s
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发表时间：
2008-02
影响因子：
4.4
通讯作者：
Lu Tie;Jian-zhao Zhang;Yan-hua Lin;T. Su;Yu-Hua Li;Hong-Li Wu;You-yi Zhang;He-ming Yu;Xue-jun Li
中科院分区：
文献类型：
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作者：
Lu Tie;Jian-zhao Zhang;Yan-hua Lin;T. Su;Yu-Hua Li;Hong-Li Wu;You-yi Zhang;He-ming Yu;Xue-jun Li
肾上腺素受体介导内源性儿茶酚胺的作用，并已被证明影响神经元发育。微管相关蛋白-2 （microtubuleassociated protein-2, MAP-2）是一种重要的细胞骨架蛋白，其响应胞外信号的磷酸化参与了神经突生长和神经元可塑性的调节。本研究旨在确定肾上腺素激活肾上腺素能受体对分化PC12细胞MAP-2磷酸化的影响，并探讨其介导机制。我们发现，在分化的PC12细胞和微管阵列中，肾上腺素可以以剂量和时间依赖的方式显著增加MAP-2c丝氨酸136位点的磷酸化。分化后的PC12细胞表达α 2a -肾上腺素受体，其拮抗剂可阻断肾上腺素的上述作用，而α 2-肾上腺素受体的激动剂可乐定可模拟肾上腺素的作用。此外，肾上腺素诱导ERK和PKC磷酸化，ERK和PKC特异性抑制剂浓度依赖地阻止肾上腺素诱导的MAP-2c在丝氨酸136位点的磷酸化。此外，用肾上腺素预处理PC12细胞部分抑制30微米诺可达唑诱导的神经突收缩。这些发现表明，肾上腺素通过α 2-肾上腺素受体介导的ERK/ pkc依赖性信号通路诱导MAP-2c在第136位的磷酸化，这可能有助于神经突的稳定。
Adrenoceptors mediate effects of endogenous catecholamines and have been shown to affect the neuronal development. Microtubule-associated protein-2 (MAP-2) is an important cytoskeleton protein whose phosphorylation in response to extracellular signal is involved in the regulation of neurite outgrowth and neuronal plasticity. The present study was designed to determine the effect of activation of adrenoceptor by epinephrine on MAP-2 phosphorylation in differentiation PC12 cells and, if so, to explore the mediating mechanism. We found that epinephrine could significantly increase the phosphorylation of MAP-2c at ser136 in a dose- and time-dependent manner in differentiated PC12 cells as well as microtubule arrays. Differentiated PC12 cells express alpha 2A-adrenoceptor, whose antagonists could block these mentioned effects of epinephrine, and clonidine which is the agonist of alpha 2-adrenoceptor could mimic the effect of epinephrine. Moreover phosphorylation of ERK and PKC was induced by epinephrine, and ERK and PKC specific inhibitors concentration-dependently prevented epinephrine-induced phosphorylation of MAP-2c at ser136. In addition, pretreatment of PC12 cells with epinephrine partly inhibited 30 microM nocodazole induced neurites retraction. These findings suggest that epinephrine induces phosphorylation of MAP-2c at ser136 through a alpha 2-adrenoceptor mediated, ERK/PKC-dependent signaling pathway, which may contribute to the stabilization of neurites.