Modulation of MAPK and NF-kappa B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats

Author(s):Show less -

Martinez, Paula F. ^{[1, 2]} ; Bonomo, Camila ^[2] ; Guizoni, Daniele M. ^[2] ; Oliveira Junior, Silvio A. ^{[1, 2]} ; Damatto, Ricardo L. ^[2] ; Cezar, Marcelo D. M. ^[2] ; Lima, Aline R. R. ^[2] ; Pagan, Luana U. ^[2] ; Seiva, Fabio R. ^[3] ; Bueno, Renata T. ^[2] ; Fernandes, Denise C. ^[4] ; Laurindo, Francisco R. ^[4] ; Zornoff, Leonardo A. M. ^[2] ; Okoshi, Katashi ^[2] ; Okoshi, Marina P. ^[2]

Affiliation

^[1] Univ Fed Mato Grosso do Sul, Campo Grande - Brazil

^[2] UNESP, Botucatu Med Sch, Botucatu, SP - Brazil

^[3] North Parana State Univ, Bandeirantes - Brazil

^[4] Heart Inst InCor HC FMUSP, Vasc Biol Lab, Sao Paulo - Brazil

• Document type: Journal article
• Source: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY; v. 39, n. 1, p. 371-384, 2016.
• Web of Science Citations: 13

Abstract

Background/Aims: 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. Methods and 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-kappa B p65 subunit was reduced; p-Ser276 in p65 and I kappa B was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-kappa B p65 subunit, but decreased p-Ser276 and p-Ser536. Conclusion: N-acetylcysteine modulates MAPK and NF-kappa B signaling pathways in soleus muscle of HF rats. (C) 2016 The Author(s) Published by S. Karger AG, Basel (AU)

• FAPESP's process: 12/07149-7 - Influence of N-acetylcysteine on apoptosis signaling in skeletal muscle of rats with chronic heart failure
• Grantee: Paula Felippe Martinez
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 12/21687-1 - Influence of N-acetylcysteine on apoptosis signaling in skeletal muscle of rats with chronic heart failure
• Grantee: Marina Politi Okoshi
• Support type: Regular Research Grants