title: Modulation of MAPK and NF-954;B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats.
abstract: OBJECTIVE
  Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats.
  
  
  RESULTS
  Four months after surgery, rats were assigned to Sham, myocardial infarction (MI)-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 ± 0.056; MI-C 0.223 ± 0.073; MI-NAC 0.136 ± 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-954;B p65 subunit was reduced; p-Ser276 in p65 and I954;B was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-954;B p65 subunit, but decreased p-Ser276 and p-Ser536.
  
  
  CONCLUSIONS
  N-acetylcysteine modulates MAPK and NF-954;B signaling pathways in soleus muscle of HF rats.
authors.affiliation: Botucatu Medical School, UNESP, Botucatu, Brazil.
authors.forename: Paula F
authors.initials: PF
authors.lastname: Martinez
authors.forename: Camila
authors.initials: C
authors.lastname: Bonomo
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Guizoni
authors.forename: Silvio A Oliveira
authors.initials: SA
authors.lastname: Junior
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Damatto
authors.forename: Marcelo D M
authors.initials: MD
authors.lastname: Cezar
authors.forename: Aline R R
authors.initials: AR
authors.lastname: Lima
authors.forename: Luana U
authors.initials: LU
authors.lastname: Pagan
authors.forename: Fabio R
authors.initials: FR
authors.lastname: Seiva
authors.forename: Renata T
authors.initials: RT
authors.lastname: Bueno
authors.forename: Denise C
authors.initials: DC
authors.lastname: Fernandes
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Laurindo
authors.forename: Leonardo A M
authors.initials: LA
authors.lastname: Zornoff
authors.forename: Katashi
authors.initials: K
authors.lastname: Okoshi
authors.forename: Marina P
authors.initials: MP
authors.lastname: Okoshi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D004452:Echocardiography; D015870:Gene Expression / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology
chemical_list: D000975:Antioxidants; D017570:MyoD Protein; D018008:Myogenin; D016328:NF-kappa B; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000111:Acetylcysteine