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) |
|---|---|
| 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 |
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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
Cite this
Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. / Shtifman, Alexander; Zhong, Nan; Lopez, Jose R.; Shen, Jie; Xu, Jin.
In: Neurobiology of Aging, Vol. 32, No. 1, 01.2011, p. 125-132.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice
AU - Shtifman, Alexander
AU - Zhong, Nan
AU - Lopez, Jose R.
AU - Shen, Jie
AU - Xu, Jin
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Ca
KW - Ca release
KW - DJ-1
KW - DJ-1 null mice
KW - Excitation-contraction coupling
KW - Resveratrol
UR - http://www.scopus.com/inward/record.url?scp=78449308039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78449308039&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2009.07.010
DO - 10.1016/j.neurobiolaging.2009.07.010
M3 - Article
VL - 32
SP - 125
EP - 132
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 1
ER -