Corticosterone activates Erk1/2 mitogen-activated protein kinase in primary hippocampal cells through rapid nongenomic mechanism  

作　　者：QIAiqun QIUJian XIAOLin CHENYizhang 

机构地区：[1]DepartmentofPhysiology,SecondMilitaryMedicalUniversity,Shanghai200433,China [2]DepartmentofPhysiology,SecondMilitaryMedicalUniversity,Shanghai200433,China [3]DepartmentofNeurobiology,SecondMilitaryMedicalUniversity,Shanghai200433,China [4]DepartmentofNeurobiology,SecondMilitaryMedicalUniversity,Shanghai200433,China／／InstituteofNeuroscience,SecondMilitaryMedicalUniversity,Shanghai200433,China

出　　处：《Progress in Natural Science:Materials International》2005年第4期325-330,共6页自然科学进展·国际材料（英文版）

基　　金：SupportedbyNationalNaturalScienceFoundationofChina (GrantNos.3 93 3 0 10 0 ;3 9840 0 19)andtheMajorStateBasicResearchDevelopmentProgramofChina (G19990 5 40 0 3 )

摘　　要：Nongenomic effects of glucocorticoids (GC) in various cell types have beenwell documented, but it still remains unknown whether the mechanism also works in hippocampus whichis a crucial target of glucocorticoids in neural system during physiologicaland/orpathophysiological processes. We present here that Corticosterone (B) could rapidly activate Erkl/2mitogen-activated protein kinase (MAPK) in primarily cultured hippocampal cells within minutes, witha bell-shaped time dependent curve which peaked at 15min and then went down to normal level in 30min. This activation was blocked by protein kinase C (PKC) inhibitor (G66976), G protein inhibitor(GDPBs), and MEK (MAPK/extracellular signal-regulated kinase kinase) inhibitor(PD98059), but not byprotein kinase A (PKA) inhibitor (H89), tyrosine kinase inhibitor (genistein), and glucocorticoidreceptor (GR) antagonist (RU38486) . Thus, the rapid activation of Erkl/2 MAPK in primaryhippocampal cells induced by B was likely mediated by a G protein coupled receptor (GPCR) pathwaywith involvement of PKC, which belonged to the nongenomic rather than genomic mechanism of GC'seffects.Nongenomic effects of glucocorticoids (GC) in various cell types have been well documented, but it still remains unknown whether the mechanism also works in hippocampus which is a crucial target of glucocorticoids in neural system during physiological and/or pathophysiological processes. We present here that corticosterone (B) could rapidly activate Erk1/2 mitogen activated protein kinase (MAPK) in primarily cultured hippocampal cells within minutes, with a bell shaped time dependent curve which peaked at 15min and then went down to normal level in 30 min. This activation was blocked by protein kinase C (PKC) inhibitor (G6976), G protein inhibitor (GDPs), and MEK(MAPK/extracellular signal regulated kinase kinase) inhibitor(PD98059), but not by protein kinase A (PKA) inbibitor (H89), tyrosine kinase inhibitor (genistein), and glucocorticoid receptor (GR) antagonist (RU38486). Thus, the rapid activation of Erk1/2 MAPK in primary hippocampal cells induced by B was likely mediated by a G protein coupled receptor (GPCR) pathway with involvement of PKC, which belonged to the nongenomic rather than genomic mechanism of GC’s effects.

关 键 词：GLUCOCORTICOID MAPK rapid effects nongenomic mechanism 

分 类 号：Q577[生物学—生物化学]