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 language | English (US) |
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Pages (from-to) | 125-132 |
Number of pages | 8 |
Journal | Neurobiology of Aging |
Volume | 32 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2011 |
Externally published | Yes |
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