Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice

Alexander Shtifman, Nan Zhong, Jose R. Lopez, Jie Shen, Jin Xu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Loss-of-function mutations in DJ-1 are associated with early-onset of Parkinson's disease. Although DJ-1 is ubiquitously expressed, the functional pathways affected by it remain unresolved. Here we demonstrate an involvement of DJ-1 in the regulation of Ca2+ homeostasis in mouse skeletal muscle. Using enzymatically dissociated flexor digitorum brevis muscle fibers from wild-type (wt) and DJ-1 null mice, we examined the effects of DJ-1 protein on resting, cytoplasmic [Ca2+] ([Ca2+]i) and depolarization-evoked Ca2+ release in the mouse skeletal muscle. The loss of DJ-1 resulted in a more than two-fold increase in resting [Ca2+]i. While there was no alteration in the resting membrane potential, there was a significant decrease in depolarization-evoked Ca2+ release from the sarcoplasmic reticulum in the DJ-1 null muscle cells. Consistent with the role of DJ-1 in oxidative stress regulation and mitochondrial functional maintenance, treatments of DJ-1 null muscle cells with resveratrol, a mitochondrial activator, or glutathione, a potent antioxidant, reversed the effects of the loss of DJ-1 on Ca2+ homeostasis. These results provide evidence of DJ-1's association with Ca2+ regulatory pathways in mouse skeletal muscle, and suggest the potential benefit of resveratrol to functionally compensate for the loss of DJ-1.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalNeurobiology of Aging
Volume32
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Fingerprint

Skeletal Muscle
Homeostasis
Null Lymphocytes
Muscle Cells
Sarcoplasmic Reticulum
Membrane Potentials
Glutathione
Parkinson Disease
Oxidative Stress
Antioxidants
Maintenance
Muscles
Mutation
resveratrol

Keywords

  • Ca
  • Ca release
  • DJ-1
  • DJ-1 null mice
  • Excitation-contraction coupling
  • Resveratrol

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. / Shtifman, Alexander; Zhong, Nan; Lopez, Jose R.; Shen, Jie; Xu, Jin.

In: Neurobiology of Aging, Vol. 32, No. 1, 01.2011, p. 125-132.

Research output: Contribution to journalArticle

Shtifman, Alexander ; Zhong, Nan ; Lopez, Jose R. ; Shen, Jie ; Xu, Jin. / Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 1. pp. 125-132.
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