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Stimulators of AMP‐activated protein kinase inhibit the respiratory burst in human neutrophils
Author(s) -
Alba Gonzalo,
El Bekay Rajaa,
Álvarez-Maqueda Moisés,
Chacón Pedro,
Vega Antonio,
Monteseirı́n Javier,
Santa Marı́a Consuelo,
Pintado Elı́zabeth,
Bedoya Francisco J.,
Bartrons Ramon,
Sobrino Francisco
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.07.077
Subject(s) - respiratory burst , respiratory system , protein kinase a , chemistry , kinase , microbiology and biotechnology , biochemistry , biology , medicine
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 (O 2 − ) 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 H 2 O 2 release, and induced the phosphorylation of c‐jun N‐terminal kinase 1 (p46), p38 mitogen‐activated 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.