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

作者：Shtifman Alexander^*; Zhong Nan; Lopez Jose R; Shen Jie; Xu Jin

来源：Neurobiology of Aging, 2011, 32(1): 125-132.

DOI：10.1016/j.neurobiolaging.2009.07.010

• DJ-1
• DJ-1 null mice
• Ca2+
• Resveratrol
• Excitation-contraction coupling
• Ca2+ release

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+]1) 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.

• 出版日期2011-1