Redox regulation in anabolic and catabolic processes.

Immunotec Research Ltd, Vaudreuil-Dorion, Québec, Canada. w.droege@immunotec.com

Current opinion in clinical nutrition and metabolic care 2006 May

Muscle wasting as it typically occurs in old age and in certain diseases is poorly understood. This review summarizes recent findings suggesting a role for redox-sensitive signaling cascades in catabolic processes. The redox-sensitive transcription factors nuclear factor kappaB and activator protein 1 facilitate ubiquitin-proteasome-dependent proteolysis. Nuclear factor kappaB also plays a role in induced expression of tumor necrosis factor alpha and other inflammatory cytokines that have been implicated in catabolic processes. The activities of nuclear factor kappaB and activator protein 1 are stimulated not only by hydrogen peroxide, which is produced in tissues by regulated enzymatic processes, but also by an oxidative shift in thiol-disulfide redox status. The oxidative shift that is typically seen in old age and certain catabolic conditions may thus play a causative role in catabolic processes. Another prominent case in point is insulin-independent 'basal' insulin receptor kinase activity, which is strongly enhanced by hydrogen peroxide or by an oxidative shift in redox status. The insulin receptor signaling cascade induces anabolic and anticatabolic effects, but its abnormal upregulation under starving conditions potentially compromises glucose and amino acid homeostasis. In genetic animal studies, impairment of insulin receptor signaling was shown to increase life span. These findings may provide a rationale for cysteine supplementation in catabolic conditions.