Activation and involvement of JNK1/2 in hydrogen peroxide-induced neurotoxicity in cultured rat cortical neurons.

Abstract:

AIM:To investigate the role of c-Jun N-terminal protein kinase 1 and 2 (JNK1/2) and the main signal pathway for its activation in hydrogen peroxide (H(2)O(2)) induced apoptotic-like cortical cell death. METHODS:Using the model of oxidative stress induced by H(2)O(2), the expression and diphosphorylation of JNK1/2 was examined by immunoblotting analysis, and neuronal apoptotic like cell death was determined by 4',6-diamidino-2-phenylindole (DAPI) staining. RESULTS:The elevation in diphosphorylation level of JNK1/2 (4.40-/5.61-fold vs sham control) was associated with the concentration of H(2)O(2) (0-100 micromol/L) and the development of apoptotic-like cell death (11.04 %-81.01 %). There was no alteration of JNK1/2 protein expression following H(2)O(2) treatment and recovery at different time points. Administration with JNK1/2 antisense oligonucleotides not only significantly decreased JNK1/2 protein expression and activation level, but also significantly reduced cortical cell death induced by H(2)O(2) exposure. Furthermore, both JNK1/2 diphosphorylation and apoptotic-like cell death were largely prevented by pretreatment with (5S,10R)-(-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801) or omission of Ca(2+) in incubation medium with ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). CONCLUSION:JNK1/2 is activated and participates in H(2)O(2)-induced apoptotic-like death in cultured rat cortical neurons mainly via N-methyl-D-aspartate (NMDA) receptor-mediated influx of extracellular Ca(2+).

journal_name

Acta Pharmacol Sin

authors

Wang W,Gao C,Hou XY,Liu Y,Zong YY,Zhang GY

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

630-6

issue

5

eissn

1671-4083

issn

1745-7254

journal_volume

25

pub_type

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