title: Hyperglycemia induced expression, phosphorylation, and translocation of αB-crystallin in rat skeletal muscle.
abstract: αB-Crystallin (αBC) is a member of the small heat shock protein family that responds to a variety of stress and prevents the aggregation of partially unfolded proteins. Chronic hyperglycemia created during diabetes results in skeletal muscle atrophy and leads to diabetic myopathy. The aim of this study was to investigate the role of αBC under chronic hyperglycemia in rat skeletal muscle. Diabetes was induced in Wistar rats by a single i.p injection of streptozotocin and maintained for a period of 12 weeks at the end of which the animals were sacrificed and the muscle was collected. The protein levels of αBC and its phosphorylation status in gastrocnemius muscle were analyzed by immunoblotting. The translocation of phosphorylated αBC was analyzed by detergent solubility assay, co-immunoprecipitation (Co-IP), and immunohistochemistry. The cell death was analyzed by TUNEL assay and by apoptotic markers. The interaction of αBC with Bax was analyzed by Co-IP. Chronic hyperglycemia significantly increased the protein levels of αBC and its phosphorylation at S59 by activation of p38 mitogen-activated protein kinase (p38MAPK) and at S45 by activation of the extracellular regulated protein kinase 1/2 (ERK1/2). Further, phosphorylated αBC translocated and interacted with desmin indicating that phosphorylated αBC forms might be involved in protection of sarcomere structures from disruption in chronic hyperglycemia. Further, Co-IP studies showed an impaired interaction of αBC with Bax which could be one of the possible factors for increased cell death as evidenced by TUNEL assay in diabetic muscle. These results suggest that an increased expression, phosphorylation, translocation of αBC, and its involvement in apoptosis might play a significant role in maintenance of cytoskeletal architecture and protection of cells from apoptosis in diabetic skeletal muscle.
authors.affiliation: Biochemistry Division, National Institute of Nutrition, Jamai-Osmania, Hyderabad, Telangana, India.
authors.forename: Vadde Sudhakar
authors.initials: VS
authors.lastname: Reddy
authors.affiliation: Biochemistry Division, National Institute of Nutrition, Jamai-Osmania, Hyderabad, Telangana, India.
authors.forename: Sneha
authors.initials: S
authors.lastname: Jakhotia
authors.affiliation: Biochemistry Division, National Institute of Nutrition, Jamai-Osmania, Hyderabad, Telangana, India.
authors.forename: P Yadagiri
authors.initials: PY
authors.lastname: Reddy
authors.affiliation: Biochemistry Division, National Institute of Nutrition, Jamai-Osmania, Hyderabad, Telangana, India.
authors.forename: G Bhanuprakash
authors.initials: GB
authors.lastname: Reddy
mesh_terms: D000818:Animals; D003459:Crystallins / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003459:Crystallins
keywords: apoptosis; diabetes; muscle; p38MAPK; phosphorylation; sHsp; αB-crystallin