title: Neuronal cells but not muscle cells are resistant to oxidative stress mediated protein misfolding and cell death: role of molecular chaperones.
abstract: Our recent study in a mouse model of familial-Amyotrophic Lateral Sclerosis (f-ALS) revealed that muscle proteins are equally sensitive to misfolding as spinal cord proteins despite the presence of low mutant CuZn-superoxide dismutase, which is considered to be the key toxic element for initiation and progression of f-ALS. More importantly, we observed differential level of heat shock proteins (Hsp's) between skeletal muscle and spinal cord tissues prior to the onset and during disease progression; spinal cord maintains significantly higher level of Hsp's compared to skeletal muscle. In this study, we report two important observations; (i) muscle cells (but not neuronal cells) are extremely vulnerable to protein misfolding and cell death during challenge with oxidative stress and (ii) muscle cells fail to mount Hsp's during challenge unlike neuronal cells. These two findings can possibly explain why muscle atrophy precedes the death of motor neurons in f-ALS mice.
authors.affiliation: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, United States; Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States.
authors.forename: Arunabh
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, United States.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Wei
authors.affiliation: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, United States.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Hamilton
authors.affiliation: Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245, United States; Department of Biochemistry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States; South Texas Veterans Health Care System, San Antonio, TX 78229, United States. Electronic address: chaudhuria@uthscsa.edu.
authors.forename: Asish R
authors.initials: AR
authors.lastname: Chaudhuri
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress; D017510:Protein Folding
chemical_list: D006360:Heat-Shock Proteins
keywords: Cell viability; Heat shock proteins; Neuron; Oxidative stress; Protein misfolding; Skeletal muscle