title: [Roles of PYK2 and caveolin-1 in alcoholic cardiomyopathy and the effect of drug intervention].
abstract: OBJECTIVE
  To explore the protein expressions of PYK2 (protein-rich tyrosine kinase-2) and caveolin-1 in alcoholic cardiomyopathy (ACM) dog model and the effect of early drug intervention.
  
  
  METHODS
  A total of 28 adult dogs were randomly divided into 4 groups: (i): alcohol-fed; (ii): alcohol plus valsartan, an angiotensin receptor blocker (ARB); (iii): alcohol plus carnitine; (iv): control group. At Month 6, the cardiac functions of all animals were evaluated by echocardiography. The concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in cardiac tissue were detected by chronometry. The protein expressions of collagen types I and III were determined by ELISA (enzyme-linked immunosorbent assay) while those of PYK2 and caveolin-1 evaluated by immunohistochemistry. The internal relationship of PYK2, caveolin-1, MDA and collagen types I & III was analyzed.
  
  
  RESULTS
  Compared with the control group, the contents of SOD and GSH-Px significantly decreased in the alcohol, valsartan and carnitine groups while MDA significantly increased in the alcohol and carnitine groups. The relative contents in each group were as follows: MDA [alcohol: (28 ± 5) U/mg Pro; valsartan: (33 ± 13) U/mg Pro; carnitine: (33 ± 10) U/mg Pro], GSH-Px [alcohol: (188 ± 37) U/g Pro; valsartan: (362 ± 29) U/g Pro; carnitine: (282 ± 29) U/g Pro and MDA [alcohol: (19.4 ± 3.0) nmol/mg Pro; carnitine: (10.8 ± 2.1) nmol/mg Pro]. Compared with the control group, the concentration of collagen typeI significantly increased in the alcohol, valsartan and carnitine groups. In the alcohol-fed group, the protein expression of PYK2 gradually increased with the progression of ACM while that of caveolin-1 stayed at a low level. Through the interventions of valsartan and carnitine, the protein expression of PYK2 significantly increased while that of caveolin-1 significantly decreased (all P < 0.01).
  
  
  CONCLUSIONS
  Alcohol promotes the myocardial oxidative stress and fibrosis through an elevated expression of PYK2 and a lowered expression of caveolin-1. Then a deterioration of cardiac structures and functions occur.
authors.affiliation: First Clinical Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sang
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Jing
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Lu
authors.forename: Qing-hui
authors.initials: QH
authors.lastname: Zhang
mesh_terms: D000108:Acetylcarnitine / Q000627:therapeutic use; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000188:drug therapy* / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D004285:Dogs; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D000108:Acetylcarnitine; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; D011493:Protein Kinase C