title: Oxidative stress, NF-κB and the ubiquitin proteasomal pathway in the pathology of calpainopathy.
abstract: The neuromuscular disorder, calpainopathy (LGMD 2A), is a major muscular dystrophy classified under limb girdle muscular dystrophies. Genetic mutations of the enzyme calpain 3 cause LGMD 2A. Calpainopathy is phenotypically observed as progressive muscle wasting and weakness. Pathomechanisms of muscle wasting of calpainopathy remain poorly understood. Oxidative stress, NF-κB and the ubiquitin proteasomal pathway underlie the pathology of several muscle wasting conditions but their role in calpainopathic dystrophy is not known. Oxidative and nitrosative stress, the source of reactive oxygen species, NF-κB signaling and protein ubiquitinylation were studied in 15 calpainopathic and 8 healthy control human muscle biopsies. Oxidative stress and NF-κB/IKK β signaling were increased in calpainopathic muscle and may contribute to increased protein ubiquitinylation and muscle protein loss. Preventing oxidative stress or inhibition of NF-κB signaling could be considered for treatment of LGMD 2A.
authors.affiliation: Neurochemistry Laboratory, Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu, India, dhanurajan@hotmail.com.
authors.forename: Dhanarajan
authors.initials: D
authors.lastname: Rajakumar
authors.forename: Mathew
authors.initials: M
authors.lastname: Alexander
authors.forename: Anna
authors.initials: A
authors.lastname: Oommen
mesh_terms: D000293:Adolescent; D002154:Calpain / Q000235:genetics; D002648:Child; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D009132:Muscles / Q000378:metabolism; D049288:Muscular Dystrophies, Limb-Girdle / Q000473:pathology* / Q000503:physiopathology; D016328:NF-kappa B / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D009573:Nitrites; D025801:Ubiquitin; D051550:I-kappa B Kinase; D002154:Calpain; D046988:Proteasome Endopeptidase Complex