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Does Serca2a Mediate the Alcohol Effects on the Heart
Author(s) -
AlRubaiee Mustafa,
Dayton Bryan,
Jeffress Miara,
Umoh Nsini,
Haddad Georges
Publication year - 2015
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.29.1_supplement.1043.10
Subject(s) - inotrope , ventricle , heart failure , medicine , endocrinology , alcohol , ejection fraction , cardiac function curve , contractility , in vivo , chemistry , cardiology , biology , biochemistry , microbiology and biotechnology
Chronic low alcohol exposure has been proven to have beneficial cardiac effects; whereas chronic high alcohol consumption could lead to heart failure. Oxidative stress is thought to be partly responsible for the alcoholic negative effects on the heart function. We have previously shown that cardiac inotropy is closely related to the activation of the survival PI3K/Akt. The objective of this study was to elucidate the signaling pathways conveying the beneficial versus the detrimental effects of chronic low and high alcohol on the heart function, respectively. Littermate adult rats were put on a 4‐months isocaloric Lieber‐Decarli liquid diet with either low alcohol (LA: 5mM) or high alcohol (HA: 100mM) levels. The measured final blood alcohol concentrations were 0.02% and 0.20% respectively. In vivo intra‐ventricular catheterization (Scisense/iWorks) of the left ventricle (LV) showed that an improved LV contractility and ejection fraction of the LA group while the opposite occurred with the HA group. in vitro cellular and sarcomeric inotropic measurements (Ionoptix) showed similar profile to the LV in vivo data. In addition, LA enhanced Ca 2+ sequestration in the sarcoplasmic reticulum whereas HA reduced it with elevation of intracellular Ca 2+ level. Our data show that improved cardiac function by LA is mediated by enhanced SERCA2 activity whereas the detrimental effects of HA are associated with reduced SERCA2a function. Funded by NIH/NIAAA 1 R15 AA019816‐01A1 and 2G12 RR003048 NIH/RCMI, DRI.