Activation of c-Jun N-terminal kinase 1 (JNK-1) after amino acid deficiency in HeLa cells.
Long-term amino acid starvation represents a form of metabolic stress which stimulates gene expression. Here we report that depriving HeLa cells for any one of a series of amino acids activates c-Jun N-terminal kinase-1 (JNK-1). In contrast, the other mitogen-activated protein kinases (MAPKs) ERK-1 and, to a lesser extent, p38 activities decreased under such conditions. In methionine- or leucine-deprived cells, JNK-1 activation occurred after 4 or 6 h, respectively, and reached a steady maximum of 5- to 7-fold over control cells afterwards. This activation was dependent on the amino acid concentration and it could be reversed by resupplying the complete medium. Limitation for all amino acids also augmented JNK-1 activity, whereas increased amino acid concentrations had an opposite effect. The free radical scavenging thiol antioxidant N-acetylcysteine (NAC) alleviated partially JNK-1 activation in amino acid-deprived cells. The data indicate that activation of JNK-1 by long-term amino acid deprivation may be mediated in part by oxidative stress.
Aubel
C
C
INRA U.R. 238 Nutrition Cellulaire et Moléculaire, 63122 Saint Gener Champanelle, France.
Dehez
S
S
Chabanon
H
H
Seva
C
C
Ferrara
M
M
Brachet
P
P
D000111:Acetylcysteine / Q000494:pharmacology; D000596:Amino Acids / Q000172:deficiency*; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D011233:Precipitin Tests; D013379:Substrate Specificity; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D000596:Amino Acids; D016166:Free Radical Scavengers; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000111:Acetylcysteine