title: Altered S-nitrosylation of p53 is responsible for impaired antioxidant response in skeletal muscle during aging.
abstract: p53 transcriptional activity has been proposed to regulate both homeostasis and sarcopenia of skeletal muscle during aging. However, the exact molecular function of p53 remains to be clearly defined. We demonstrated a requirement of nuclear p53 S-nitrosylation in inducing a nitric oxide/PGC-1α-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear S-nitrosylation and failed in inducing the expression of antioxidant genes (i.e. SOD2 and GCLC). Moreover, we found that during aging the nuclear S-nitrosylation of p53 significantly declines in gastrocnemius/soleus leading to an impairment of redox homeostasis of skeletal muscle. We suggested that decreased level of nuclear neuronal nitric oxide synthase (nNOS)/Syntrophin complex, which we observed during aging, could be responsible for impaired nuclear S-nitrosylation. Taken together, our data indicate that altered S-nitrosylation of p53 during aging could be a contributing factor of sarcopenia condition and of other skeletal muscle pathologies associated with oxidative/nitrosative stress.
authors.affiliation: Università Telematica San Raffaele Roma, Rome, Italy.|IRCCS San Raffaele 'La Pisana', Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.affiliation: Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.|IRCCS San Raffaele 'La Pisana', Rome, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide
keywords: S-nitrosylation; aging; antioxidant; atrophy; sarcopenia