In inclusion-body myositis muscle fibers Parkinson-associated DJ-1 is increased and oxidized.
Sporadic inclusion-body myositis (s-IBM) is the most common muscle disease of older persons. The muscle-fiber molecular phenotype exhibits similarities to both Alzheimer-disease (AD) and Parkinson-disease (PD) brains, including accumulations of amyloid-beta, phosphorylated tau, alpha-synuclein, and parkin, as well as evidence of oxidative stress and mitochondrial abnormalities. Early-onset autosomal-recessive PD can be caused by mutations in the DJ-1 gene, leading to its inactivation. DJ-1 has antioxidative and mitochondrial-protective properties. In AD and PD brains, DJ-1 is increased and oxidized. We studied DJ-1 in 17 s-IBM and 18 disease-control and normal muscle biopsies by: (1) immunoblots of muscle homogenates and mitochondrial fractions; (2) real-time PCR; (3) oxyblots evaluating DJ-1 oxidation; (4) light- and electron-microscopic immunocytochemistry. Compared to controls, in s-IBM muscle fibers DJ-1 was: (a) increased in the soluble fraction, monomer 2-fold (P = 0.01), and dimer 2.8-fold (P = 0.004); (b) increased in the mitochondrial fraction; (c) highly oxidized; and (d) aggregated in about 15% of the abnormal muscle fibers. DJ-1 mRNA was increased 3.5-fold (P = 0.034). Accordingly, DJ-1 might play a role in human muscle disease, and thus not be limited to human CNS degenerations. In s-IBM muscle fibers, DJ-1 could be protecting these fibers against oxidative stress, including protection of mitochondria.
Terracciano
Chiara
C
Department of Neurology, USC Neuromuscular Center, University of Southern California Keck School of Medicine, Good Samaritan Hospital, 637 S. Lucas Avenue, Los Angeles, CA 90017-1912, USA.
Nogalska
Anna
A
Engel
W King
WK
Wojcik
Slawomir
S
Askanas
Valerie
V
D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000378:metabolism*; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1