Title | Epinephrine increases phosphorylation of MAP-2c in rat pheochromocytoma cells (PC12 cells) via a protein kinase c- and mitogen activated protein kinase-dependent mechanism |
Authors | Tie, Lu Zhang, Jian-Zhao Lin, Yan-Hua Su, Tian-Hao Li, Yu-Hua Wu, Hong-Li Zhang, You-Yi Yu, He-Ming Li, Xue-Jun |
Affiliation | Peking Univ, Dept Pharmacol, Sch Basic Med Sci, Beijing 100083, Peoples R China. Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China. Peking Univ Third Hosp, Inst Vasc Med, Key Lab Mol Cardiovasc Sci, Minist Educ, Beijing 100083, Peoples R China. Natl Res Inst Family Planning, Beijing 100081, Peoples R China. Peking Univ, Dept Pharmacol, Sch Basic Med Sci, 38 Xueyuan Rd, Beijing 100083, Peoples R China. |
Keywords | microtubule-associated protein 2c phosphorylation alpha(2)-andrenoceptor ERK PKC PC12 cells Phi AP18 MICROTUBULE-ASSOCIATED PROTEIN-2 MESSENGER-RNA EXPRESSION BRAIN-DEVELOPMENT ALPHA(2)-ADRENOCEPTOR AGONISTS DIFFERENTIAL EXPRESSION ALPHA(2) ADRENOCEPTORS MAP2 PHOSPHORYLATION NEURITE OUTGROWTH NEURONS DEXMEDETOMIDINE |
Issue Date | 2008 |
Publisher | 蛋白代谢研究杂志 |
Citation | JOURNAL OF PROTEOME RESEARCH.2008,7,(4),1704-1711. |
Abstract | 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 mu M 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. |
URI | http://hdl.handle.net/20.500.11897/156940 |
ISSN | 1535-3893 |
DOI | 10.1021/pr700711s |
Indexed | SCI(E) PubMed |
Appears in Collections: | 药学院 第三医院 天然药物与仿生药物国家重点实验室 |