The regulation of AMP-activated protein kinase by H2O2.

Citation
Sl. Choi et al., The regulation of AMP-activated protein kinase by H2O2., BIOC BIOP R, 287(1), 2001, pp. 92-97
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
287
Issue
1
Year of publication
2001
Pages
92 - 97
Database
ISI
SICI code
0006-291X(20010914)287:1<92:TROAPK>2.0.ZU;2-1
Abstract
AMP-activated protein kinase (AMPK), a heterotrimeric serine/threonine kina se, is activated by conditions leading to an increase of the intracellular AMP: ATP ratio. However, how AMPK is regulated under the oxidative stress i s completely unknown. In the present study, we examined effects of the oxid ative agent H2O2 on AMPK. AMPK was transiently and concentration-dependentl y activated by H2O2 in NIH-3T3 cells. This activation was tightly associate d with an increased AMP:ATP ratio, an electrophoretic mobility shift of AMP K al catalytic subunit, and an increased phosphorylation level of AMPK alph a1 threonine 172, which is a major in vitro phosphorylation site by the ups tream AMPK kinase. All of these events were significantly blocked by the pr etreatment of 0.5% dimethyl sulfoxide, a potent hydroxyl radical scavenger, indicating that AMPK cascades are highly sensitive to the oxidative stress . Interestingly, a specific tyrosine kinase inhibitor, genistein, further s timulated the H2O2-induced AMPK activity by 70% without altering the AMP:AT P. Taken together, our results suggest that AMP:ATP ratio is the major para meter to which AMPK responds under the oxidative stress, but AMPK may be re gulated in part by a tyrosine kinase-dependent pathway, which is independen t of the cellular adenosine nucleotides level. (C) 2001 Academic Press.