Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice.
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 Ca(2+) 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 [Ca(2+)] ([Ca(2+)](i)) and depolarization-evoked Ca(2+) release in the mouse skeletal muscle. The loss of DJ-1 resulted in a more than two-fold increase in resting [Ca(2+)](i). While there was no alteration in the resting membrane potential, there was a significant decrease in depolarization-evoked Ca(2+) 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 Ca(2+) homeostasis. These results provide evidence of DJ-1's association with Ca(2+) regulatory pathways in mouse skeletal muscle, and suggest the potential benefit of resveratrol to functionally compensate for the loss of DJ-1.
Shtifman
Alexander
A
Department of Neurology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, 736 Cambridge St., CBR-406, Boston, MA 02135, USA. alex.shtifman@caritaschristi.org
Zhong
Nan
N
Lopez
Jose R
JR
Shen
Jie
J
Xu
Jin
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D015513:Oncogene Proteins / Q000172:deficiency*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D000077185:Resveratrol; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology
D000975:Antioxidants; C506944:Atp2a1 protein, mouse; D015513:Oncogene Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D013267:Stilbenes; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000077185:Resveratrol; D002118:Calcium
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