title: Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice.
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 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.
authors.affiliation: 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
authors.forename: Alexander
authors.initials: A
authors.lastname: Shtifman
authors.forename: Nan
authors.initials: N
authors.lastname: Zhong
authors.forename: Jose R
authors.initials: JR
authors.lastname: Lopez
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: 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
chemical_list: 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
references.citation: Muscle Nerve. 1986 Jan;9(1):85-6
references.pmid: 3951486
references.citation: Science. 2003 Jan 10;299(5604):256-9
references.pmid: 12446870
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5215-20
references.pmid: 15784737
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14807-12
references.pmid: 17766438
references.citation: Neurobiol Aging. 2010 Dec;31(12):2080-90
references.pmid: 19108934
references.citation: Antioxid Redox Signal. 2000 Spring;2(1):35-40
references.pmid: 11232597
references.citation: J Physiol. 1981 Jun;315:531-48
references.pmid: 6273543
references.citation: Mol Cell. 2009 Mar 13;33(5):627-38
references.pmid: 19285945
references.citation: Muscle Nerve. 1999 Dec;22(12):1674-83
references.pmid: 10567080
references.citation: Cell. 2006 Oct 20;127(2):397-408
references.pmid: 17055439
references.citation: Neuron. 2009 Apr 30;62(2):218-29
references.pmid: 19409267
references.citation: Anesthesiology. 2006 Dec;105(6):1164-75
references.pmid: 17122579
references.citation: Biochem Biophys Res Commun. 2004 May 7;317(3):722-8
references.pmid: 15081400
references.citation: J Biol Chem. 2001 Oct 5;276(40):37556-63
references.pmid: 11477070
references.citation: J Neurosci Methods. 1981 Jun;4(1):73-86
references.pmid: 7253701
references.citation: Cell. 1999 Jul 9;98(1):115-24
references.pmid: 10412986
references.citation: Neuron. 2005 Feb 17;45(4):489-96
references.pmid: 15721235
references.citation: Hum Mol Genet. 2008 Nov 1;17(21):3357-67
references.pmid: 18689799
references.citation: Curr Opin Neurobiol. 2007 Jun;17(3):331-7
references.pmid: 17499497
references.citation: Biochemistry. 1986 Jan 14;25(1):236-44
references.pmid: 3754147
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8
references.pmid: 15181200
references.citation: Mol Cancer Res. 2003 Feb;1(4):247-61
references.pmid: 12612053
references.citation: J Physiol. 2001 Dec 15;537(Pt 3):763-78
references.pmid: 11744753
references.citation: Hum Mol Genet. 2005 May 1;14(9):1231-41
references.pmid: 15790595
references.citation: Anesthesiology. 1992 May;76(5):711-9
references.pmid: 1575338
references.citation: Nature. 2006 Nov 16;444(7117):337-42
references.pmid: 17086191
references.citation: Free Radic Biol Med. 2008 Sep 15;45(6):773-9
references.pmid: 18601999
references.citation: Biochim Biophys Acta. 1995 May 8;1241(1):59-116
references.pmid: 7742348
references.citation: FASEB J. 2006 Oct;20(12):2165-7
references.pmid: 16940437
references.citation: EMBO Rep. 2004 Feb;5(2):213-8
references.pmid: 14749723
references.citation: J Biol Chem. 2004 Dec 17;279(51):53524-32
references.pmid: 15385569
references.citation: J Biol Chem. 2001 May 11;276(19):15625-30
references.pmid: 11278999
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15091-6
references.pmid: 17015834
references.citation: J Physiol. 1996 Jun 1;493 ( Pt 2):309-15
references.pmid: 8782098
references.citation: Nature. 2004 Aug 5;430(7000):686-9
references.pmid: 15254550
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7217-22
references.pmid: 17438283
references.citation: J Physiol. 2004 Oct 15;560(Pt 2):451-68
references.pmid: 15308682
references.citation: Brain. 2004 Feb;127(Pt 2):420-30
references.pmid: 14662519
references.citation: Neurobiol Dis. 2008 Mar;29(3):505-14
references.pmid: 18187333
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12517-22
references.pmid: 16894167
references.citation: J Biol Chem. 2006 Apr 21;281(16):10816-24
references.pmid: 16517609
references.citation: J Physiol. 1999 Oct 1;520 Pt 1:203-15
references.pmid: 10517812