Heavy long-term ethanol consumption induces an alpha- to beta-myosin heavy chain isoform transition in rat |
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| Authors: | Julia Meehan Mariann R Piano R John Solaro John M Kennedy |
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| Institution: | (1) University of Illinois at Chicago, Department of Physiology and Biophysics, 835 S. Wolcott Ave., Mail Code 901, Chicago, IL 60612, USA, Email: Jkennedy@uic.edu, US;(2) University of Illinois at Chicago, Department of Medical and Surgical Nursing, 845 S. Damen Ave., Mail Code 802, Chicago, IL 60612, USA, US |
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| Abstract: | Alcoholic heart muscle disease is characterized by structural changes which include chamber dilation, ventricular hypertrophy,
and myocyte damage. These effects often lead to contractile dysfunction and ultimately to heart failure if alcohol consumption
is not terminated. In rat models for heart failure in which heart failure is induced by pressure or volume overload, there
is a shift in the myosin heavy chain (MHC) isoforms, from α to β. As a result of this MHC transition, there is typically a
decrease in myosin ATPase activity. We utilized a rat model of chronic alcohol consumption in order to determine if alcohol
causes a similar shift in MHC isoforms and changes in myosin ATPase activity. A liquid diet containing 9% ethanol (46% of
daily calories; 11.8 g/kg/day) was administered to adult rats for a period of 60 or 90 days. This heavy consumption of ethanol
resulted in an average blood ethanol content of 150 mg%. The relative abundance of β-MHC isoform protein increased from a
control level of 9.7% to 35.1% in hearts of ethanol-fed rats, following 90 days of ethanol consumption. In a separate set
of experiments, the levels of α-MHC and β-MHC mRNA were demonstrated to increase by 150% and 230%, respectively. Following
a 60 day treatment, there was a significant reduction in the actomyosin Mg2+-ATPase activity in the myofibrillar preparations from hearts of ethanol-fed rats compared to hearts from control-fed rats.
In addition, the myosin Ca2+-ATPase activity was decreased 17% and 30% after 60 and 90 days of ethanol consumption, respectively. The present study demonstrates
that chronic ethanol consumption induces an increase in the proportion of the total MHC content composed of the β-isoform.
This isoform transition is accompanied by an accumulation of β-MHC mRNA, suggesting that the switch is organized pretranslationally.
A functional consequence of this transition in MHC phenotype is demonstrated by significant decreases in the myofibrillar
and myosin ATPase activities.
Received: 17 November 1998, Returned for 1. revision: 4 January 1999, 1. Revision received: 22 March 1999, Returned for 2.
Revision: 12 April 1999, 2. Revision received: 31 May, Accepted: 31 May 1999 |
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| Keywords: | Heart – ethanol – myosin heavy chain – myofibrillar ATPase – mRNA – rat |
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