Alcoholism reduces male heart's ability to synthesize protein; possible therapy target?

03/30/05

Altered protein factor phosphorylation may point to therapy target

San Diego (April 3, 2005) – The fact that men and women react differently to alcohol consumption and addiction, health and behavior risks, disease and death is well known and accepted. Women get drunker faster on less alcohol than men, but fewer women drink either occasionally or heavily, and men are more likely to become dependent on alcohol.

However the theories on the cause of those differences vary widely. Research studies and surveys often yield conflicting results. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) strategic plan on health disparities notes that "Chronic alcohol abuse can result in alcoholic cardiomyopathy (ACM), and there, too disparities appear to exist" in terms of causes or propensity among different populations.

*Paper presentation: "Gender modulates the response to chronic alcohol intoxication in the heart," 12:30 p.m.-3 p.m. Tuesday April 5, Physiology 909.5 /board #A130. On view 7:30 a.m. - 4 p.m.

Thomas C. Vary is presenting the research at the 35th Congress of the International Union of Physiological Sciences in San Diego, March 31 - April 5, 2005.

Alcoholism: Scope of death and overall cost in the U.S.

ACM is an important cause of mortality among people suffering from alcoholism. It's estimated that least 500,000 deaths per year can be attributed to alcohol abuse in the United States, while as much as 20% of total U.S. health care expenditures in the US may be related to excessive ethanol consumption in one form or another.

According to a report in the journal "Chest" in the U.S., "in both sexes and all races, long-term heavy alcohol consumption (of any beverage type) is the leading cause of a nonischemic, dilated cardiomyopathy" or ACM. A study in an NIAAA publication reports that the amount of alcohol necessary to produce the kind of structural and functional heart abnormalities seen in ACM is "eight or more drinks per day over a period of 20 years." It adds that "the prevalence of ACM is lower in women than men, yet women may be more vulnerable to ACM," since some reports say that ACM develops in women with a lower total lifetime exposure to alcohol."

Penn State physiologists test role of protein metabolism, synthesis

Researchers at Pennsylvania State University College of Medicine's Cellular and Molecular Physiology Department decided to examine the metabolic basis of ACM, also called alcoholic heart muscle disease. They thought "defects in myocardial protein metabolism were probably a contributing factor for the precipitation and progress of the disease," according to Thomas C. Vary, the lead researcher, working with Joseph M. Leese, an undergraduate summer research fellow and Scot R. Kimball. Changes in protein metabolism would be expected to influence the expression of proteins that are needed for normal structure and function in the heart. Changes in protein expression could lead to structural and/or functional defects in the heart.

The Penn State researchers decided to compare the effects of prolonged alcohol consumption on protein metabolism between males and females in a model of alcoholism. Chronic alcohol consumption was mimicked by supplying the equivalent of a liter of wine a day in both food and drinking water. "What we observed was that there were gender differences in how the heart is able to synthesize proteins both in controls and alcoholism," Vary said. "In controls, the ability of the heart muscle to synthesize proteins was lower in females than in males. Females also had smaller hearts."

Male heart muscle protein synthesis declines after 26 weeks of high alcohol use

Moreover "with prolonged alcohol consumption over 26 weeks, the ability of the heart muscle to synthesize proteins was compromised in males, but not in females," Vary noted. Going a step further, they examined "the metabolic pathways involved in protein synthesis.

"We found that one particular step in the process of protein synthesis was affected in males but not females following prolonged ethanol consumption," Vary said. "Furthermore it appeared that the defect resulted from altered phosphorylation of a particular protein factor involved in protein synthesis, and the alterations in protein metabolism mirrored alcohol-induced defects in ventricular function."

Next steps: Vary said: "Future research will be directed at developing potential therapeutic modalities that prevent the alcohol-induced defects in protein synthesis."

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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