Age-Dependent Oxidative Stress Elevates Arginase 1 and Uncoupled Nitric Oxide Synthesis in Skeletal Muscle of Aged Mice

Chirayukumar D Pandya, Byung Lee, Haroldo Alfredo Flores Toque, Bharati Mendhe, Robert T. Bragg, Bhaumik Pandya, Reem T. Atawia, Carlos M Isales, Mark W Hamrick, R. William Caldwell, Sadanand T Fulzele

Research output: Contribution to journalArticle

Abstract

Aging is associated with reduced muscle mass (sarcopenia) and poor bone quality (osteoporosis), which together increase the incidence of falls and bone fractures. It is widely appreciated that aging triggers systemic oxidative stress, which can impair myoblast cell survival and differentiation. We previously reported that arginase plays an important role in oxidative stress-dependent bone loss. We hypothesized that arginase activity is dysregulated with aging in muscles and may be involved in muscle pathophysiology. To investigate this, we analyzed arginase activity and its expression in skeletal muscles of young and aged mice. We found that arginase activity and arginase 1 expression were significantly elevated in aged muscles. We also demonstrated that SOD2, GPx1, and NOX2 increased with age in skeletal muscle. Most importantly, we also demonstrated elevated levels of peroxynitrite formation and uncoupling of eNOS in aged muscles. Our in vitro studies using C2C12 myoblasts showed that the oxidative stress treatment increased arginase activity, decreased cell survival, and increased apoptotic markers. These effects were reversed by treatment with an arginase inhibitor, 2(S)-amino-6-boronohexanoic acid (ABH). Our study provides strong evidence that L-arginine metabolism is altered in aged muscle and that arginase inhibition could be used as a novel therapeutic target for age-related muscle complications.

Original languageEnglish (US)
Number of pages1
JournalOxidative medicine and cellular longevity
Volume2019
DOIs
StatePublished - Jan 1 2019

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Arginase
Oxidative stress
Muscle
Nitric Oxide
Skeletal Muscle
Oxidative Stress
Muscles
Myoblasts
Bone
Aging of materials
Cell Survival
Sarcopenia
Cells
Bone and Bones
Peroxynitrous Acid
Bone Fractures
Osteoporosis
Arginine
Metabolism
Cell Differentiation

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

Cite this

Age-Dependent Oxidative Stress Elevates Arginase 1 and Uncoupled Nitric Oxide Synthesis in Skeletal Muscle of Aged Mice. / Pandya, Chirayukumar D; Lee, Byung; Flores Toque, Haroldo Alfredo; Mendhe, Bharati; Bragg, Robert T.; Pandya, Bhaumik; Atawia, Reem T.; Isales, Carlos M; Hamrick, Mark W; Caldwell, R. William; Fulzele, Sadanand T.

In: Oxidative medicine and cellular longevity, Vol. 2019, 01.01.2019.

Research output: Contribution to journalArticle

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