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Regulation of SERCA2a by chronic ethanol: role of Akt (864.8)
Author(s) -
Jeffress Miara,
Umoh Nsini,
Haddad Georges
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.864.8
Subject(s) - phospholamban , protein kinase b , alcoholic cardiomyopathy , contractility , phosphorylation , endocrinology , dilated cardiomyopathy , endoplasmic reticulum , medicine , western blot , chemistry , sarcoplasm , cardiomyopathy , transfection , calcium , heart failure , biochemistry , gene
Alcoholic cardiomyopathy is one of the leading causes of non‐ischemic dilated cardiomyopathy accounting for 36% of cases. Almost 50% of alcoholics develop this disease. Previously our lab has demonstrated the up‐regulation of intracellular Ca 2+ (IC) in dilated cardiomyopathy by Akt. Here we investigate the role of Akt in regulating Ca 2+ cycling proteins and contractility in chronic ethanol exposed cardiocytes. Parallel measures of IC and sarcomere/cellular contractions were assessed (Ionoptix) with the expression level (western blot) of Ca 2+ handling proteins (sarcoplasmic reticulum calcium ATPase(SERCA2a), phospholamban(PLN), Na + ‐Ca 2+ exchanger (NCX) and L‐type Ca 2+ channels(LTCC)) from control, low (LA: 0.02%), and high (HA: 0.45%) alcoholic rat hearts (4 months on Lieber DiCarli liquid diet), with and without Ad.EGFP and Ad.Akt transfection. Our results show an inotropically damaging increase in IC with HA but not with LA. In parallel, NCX protein expression is diminished in HA whereas that of LTCCs is increased. In addition, SERCA2a levels are increased in LA and decreased in HA. Upon Ad.Akt transfection SERCA2a levels increased in HA. Protein levels of phosphorylated PLN also increased in LA and decreased in HA hearts. This suggests that chronic ethanol elevates IC to harmful levels through cytoplasmic trapping via NCX which is exacerbated by reduced SERCA2a through PLN in an Akt‐dependent manner. Grant Funding Source : Supported by NIH/NIAAA/1R15AAA019816‐01A1 and 2G12 RR003048