Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived Snell dwarf mice
作者： Ching‐Chyuan Hsieh , John Papaconstantinou
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摘要: We have proposed that the age-associated increase of reactive oxygen species (ROS) by electron transport chain (ETC) dysfunction may cause elevated basal level p38 MAPK stress response pathway activity. However, mechanism which ROS activates this is not clear. Here we propose activation complex I (CI) generated ROS, in to rotenone (ROT) treatment, based on ability reduced Trx bind and inhibit ASK 1 its release from upon oxidation. This balance free vs. bound ASK1 regulates To support demonstrate production ROT treated AML12 hepatocyte cells dissociates Trx-ASK1 complex, thereby increasing supported N-acetyl cysteine (NAC) prevent dissociation pathway. also demonstrated ratio ASK1/Trx-ASK1 increases aged mouse livers correlates with increased activity The longevity Snell dwarf mice has been attributed their resistance oxidative stress. A comparison levels young dwarfs showed a higher abundance than age-matched controls. These results, are indicative decreased stress, suggest liver alter Trx-ASK1,
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