Altered S-nitrosylation of p53 is responsible for impaired antioxidant response in skeletal muscle during aging

Research output: Contribution to journalArticle

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-1a-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear Snitrosylation 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.

Original languageEnglish
Pages (from-to)3450-3467
Number of pages18
JournalAging
Volume8
Issue number12
DOIs
Publication statusPublished - 2016

Fingerprint

Skeletal Muscle
Antioxidants
Sarcopenia
Homeostasis
Nitric Oxide Synthase Type I
Oxidation-Reduction
Nitric Oxide
Oxidative Stress
Pathology
Gene Expression
DNA

Keywords

  • Aging
  • Antioxidant
  • Atrophy
  • S-nitrosylation
  • Sarcopenia

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Cite this

@article{16cc449e69254fc696614cb7b7f6ccd4,
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-1a-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear Snitrosylation 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.",
keywords = "Aging, Antioxidant, Atrophy, S-nitrosylation, Sarcopenia",
author = "Sara Baldelli and Ciriolo, {Maria Rosa}",
year = "2016",
doi = "10.18632/aging.101139",
language = "English",
volume = "8",
pages = "3450--3467",
journal = "Aging",
issn = "1945-4589",
publisher = "US Administration on Aging",
number = "12",

}

TY - JOUR

T1 - Altered S-nitrosylation of p53 is responsible for impaired antioxidant response in skeletal muscle during aging

AU - Baldelli, Sara

AU - Ciriolo, Maria Rosa

PY - 2016

Y1 - 2016

N2 - 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-1a-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear Snitrosylation 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.

AB - 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-1a-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear Snitrosylation 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.

KW - Aging

KW - Antioxidant

KW - Atrophy

KW - S-nitrosylation

KW - Sarcopenia

UR - http://www.scopus.com/inward/record.url?scp=85010576304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010576304&partnerID=8YFLogxK

U2 - 10.18632/aging.101139

DO - 10.18632/aging.101139

M3 - Article

AN - SCOPUS:85010576304

VL - 8

SP - 3450

EP - 3467

JO - Aging

JF - Aging

SN - 1945-4589

IS - 12

ER -