Nicholas S Aberle1, Larry Burd, Bonnie H Zhao, Jun Ren. 1. Deparment of Pharmacology, Physiology and Therapeutics, Univeresity of North Dakota School of Medicine and Health Science, Grand Forks, ND 58203, USA.
Abstract
AIMS: Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy characterized by impaired ventricular contractility. This study was designed to examine the effect of group B vitamin supplementation on short-term exposure of the main alcohol metabolite acetaldehyde (ACA)-induced cardiac contractile dysfunction in rat ventricular myocytes. METHODS: Mechanical contractile properties were evaluated by an IonOptix SoftEdge system. Protein damage and apoptosis were determined by protein carbonyl and caspase-3 assays, respectively. RESULTS: Short-term (4-6 h) culture of myocytes with ACA (10 microM) depressed peak shortening amplitude, maximal velocity of shortening/relengthening, shortened duration of shortening but not the duration of relengthening. ACA exposure also enhanced protein carbonyl formation and apoptosis in ventricular myocytes. The toxin-induced mechanical defects, protein damage and apoptosis were ablated by vitamin B1 (10 microM), an essential vitamin required for DNA synthesis and repair. Vitamin B6 (10 microM) attenuated ACA-induced impairment of shortening duration. Vitamin B12 (1 mM) attenuated ACA-induced reduction in maximal velocity of shortening/relengthening. Unlike vitamin B1, none of the other ACA-elicited alterations in myocyte mechanical function were affected by vitamin B6 or vitamin B12. Vitamin B6 and vitamin B12 partially, but significantly, attenuated the ACA-induced carbonyl formation without affecting ACA-induced apoptosis. CONCLUSIONS: These data provide evidence that vitamin B1 supplementation may be protective for ACA-induced cytotoxicity through protection against protein damage and apoptotic cell death in ventricular myocytes.
AIMS: Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy characterized by impaired ventricular contractility. This study was designed to examine the effect of group B vitamin supplementation on short-term exposure of the main alcohol metabolite acetaldehyde (ACA)-induced cardiac contractile dysfunction in rat ventricular myocytes. METHODS: Mechanical contractile properties were evaluated by an IonOptix SoftEdge system. Protein damage and apoptosis were determined by protein carbonyl and caspase-3 assays, respectively. RESULTS: Short-term (4-6 h) culture of myocytes with ACA (10 microM) depressed peak shortening amplitude, maximal velocity of shortening/relengthening, shortened duration of shortening but not the duration of relengthening. ACA exposure also enhanced protein carbonyl formation and apoptosis in ventricular myocytes. The toxin-induced mechanical defects, protein damage and apoptosis were ablated by vitamin B1 (10 microM), an essential vitamin required for DNA synthesis and repair. Vitamin B6 (10 microM) attenuated ACA-induced impairment of shortening duration. Vitamin B12 (1 mM) attenuated ACA-induced reduction in maximal velocity of shortening/relengthening. Unlike vitamin B1, none of the other ACA-elicited alterations in myocyte mechanical function were affected by vitamin B6 or vitamin B12. Vitamin B6 and vitamin B12 partially, but significantly, attenuated the ACA-induced carbonyl formation without affecting ACA-induced apoptosis. CONCLUSIONS: These data provide evidence that vitamin B1 supplementation may be protective for ACA-induced cytotoxicity through protection against protein damage and apoptotic cell death in ventricular myocytes.
Authors: Daniel M Spielman; Dirk Mayer; Yi-Fen Yen; James Tropp; Ralph E Hurd; Adolf Pfefferbaum Journal: Magn Reson Med Date: 2009-08 Impact factor: 4.668