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

NEUROBIOLOGY OF AGING

卷:32

Article

Shtifman, Alexander¹  Zhong, Nan¹  Lopez, Jose R.^2,3  Shen, Jie⁴  Xu, Jin¹ 

[1] Tufts Univ, Sch Med, Caritas St Elizabeths Med Ctr, Dept Neurol, Boston, MA 02135 USA

[2] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesia, Sch Med, Boston, MA 02115 USA

[3] IVIC, Ctr Biofis & Bioquim, Caracas, Venezuela

[4] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA

关键词: DJ-1;    DJ-1 null mice;    Ca2+;    Resveratrol;    Excitation-contraction coupling;    Ca2+ release;   

DOI  :  10.1016/j.neurobiolaging.2009.07.010

来源: Elsevier

【 摘 要 】

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. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

Free