Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice.
Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice.
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DOI：
10.1016/j.neurobiolaging.2009.07.010
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发表时间：
2011-01
影响因子：
4.2
通讯作者：
Xu, Jin
中科院分区：
文献类型：
--
作者：
Shtifman, Alexander;Zhong, Nan;Lopez, Jose R.;Shen, Jie;Xu, Jin
DJ - 1的功能缺失突变与帕金森病的早发相关尽管DJ - 1广泛表达，但受其影响的功能途径仍未解决。在这里，我们证明了DJ - 1参与调节小鼠骨骼肌中的Ca 2+稳态。使用酶促解离的屈趾短肌肌纤维从野生型（wt）和DJ - 1基因敲除小鼠，我们研究了DJ - 1蛋白对小鼠骨骼肌静息，细胞质[Ca 2 +]（[Ca 2 +]i）和去极化诱发的Ca 2+释放的影响。DJ - 1的缺失导致静息[Ca 2 +]i增加两倍以上。虽然静息膜电位没有改变，但去极化诱发的DJ - 1空肌细胞肌浆网Ca 2+释放显著减少。与DJ - 1在氧化应激调节和线粒体功能维持中的作用一致，用白藜芦醇（一种线粒体激活剂）或谷胱甘肽（一种有效的抗氧化剂）治疗DJ - 1无效的肌细胞，逆转了DJ - 1丧失对Ca 2+稳态的影响。这些结果提供了DJ - 1与小鼠骨骼肌中Ca 2+调节途径相关的证据，并表明白藜芦醇在功能上补偿DJ - 1损失的潜在益处。
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.
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影响因子：
5.5
作者：
Blazev, R;Lamb, GD
通讯作者：
Lamb, GD
影响因子：
2.9
作者：
MEISSNER, G;DARLING, E;EVELETH, J
通讯作者：
EVELETH, J
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
6.1
作者：
Chandran, Jayanth S.;Lin, Xian;Cai, Huaibin
通讯作者：
Cai, Huaibin
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.