Alba, G , El Bekay, R , Alvarez-Maqueda, M , CHACON FERNANDEZ, PEDRO JOSE, Vega, A , Monteseirín, J , María, CS , Pintado, E , Bedoya, FJ , Bartrons, R , Sobrino, F
No
FEBS Lett.
Article
Científica
3.843
2.356
27/08/2004
000223697200037
In the present study, we have examined the potential ability of 5'-AMP-activated protein kinase (AMPK) to modulate NADPH oxidase activity in human neutrophils. AMPK activated with either 5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) or with 5'-AMP significantly attenuated both phorbol 12-myristate 13-acetate (PMA) and formyl methionyl leucyl phenylalanine-stimulated superoxide anion (02) release by human neutrophils, consistently with a reduced translocation to the cell membrane and phosphorylation of a cytosolic component of NADPH oxidase, namely p47(phox). AMPK was found to be present in human neutrophils and to become phosphorylated in response to either AICAR or other stimulators of its enzyme activity. Furthermore, AICAR also strongly reduced PMA-dependent H2O2 release, and induced the phosphorylation of c-jun N-terminal kinase 1 (p46), p38 mitogenactivated protein kinase and extracellular signal-regulated kinase. Present data demonstrate for the first time that the activation of AMPK, in states of low cellular energy charge (such as under high levels of 5'-AMP) or other signals, could be a factor contributing to reduce the host defense mechanisms. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
adenine nucleotide; 5 '-AMP-activated protein kinase; NADPH-oxidase; superoxide anion