Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy.
To identify proteins expressed abnormally in facioscapulohumeral muscular dystrophy (FSHD), we extracted soluble proteins from deltoid muscle biopsies from unaffected control and FSHD patients and analyzed them using two-dimensional electrophoresis, mass spectrometry and immunoblotting. Muscles from patients with FSHD showed large increases over controls in a single soluble, 34 kDa protein (pI=5.08) identified by mass spectrometry and immunoblotting as mu-crystallin (CRYM). Soluble fractions of biopsies of several other myopathies and muscular dystrophies showed no appreciable increases in mu-crystallin. Mu-crystallin has thyroid hormone and NADPH binding activity and so may influence differentiation and oxidative stress responses, reported to be altered in FSHD. It is also linked to retinal and inner ear defects, common in FSHD, suggesting that its up-regulation may play a specific and important role in pathogenesis of FSHD.
Reed
Patrick W
PW
Department of Physiology, University of Maryland School of Medicine, 660 W. Redwood Street, Baltimore, MD 21201, USA.
Corse
Andrea M
AM
Porter
Neil C
NC
Flanigan
Kevin M
KM
Bloch
Robert J
RJ
D001706:Biopsy; D003459:Crystallins / Q000096:biosynthesis*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D015151:Immunoblotting; D018482:Muscle, Skeletal / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D012394:Rosaniline Dyes; D016622:Silver Staining; D015854:Up-Regulation / Q000502:physiology; D000090803:mu-Crystallins
C000716469:CRYM protein, human; D003459:Crystallins; D012394:Rosaniline Dyes; C048139:Coomassie blue; D000090803:mu-Crystallins