03 December 2013

Drink, yes FOXO3 understand!

Transcription factor protects the liver from alcohol

ABC Magazine based on Elsevier materials:
Transcription Factor May Protect Against Hepatic Injury Caused by Hepatitis C and AlcoholResearchers from the University of Kansas Medical Center have found that the transcription factor FOXO3 helps protect the liver from the damaging effects of alcohol.

In addition, it was found that the combined effects of hepatitis C virus and ethanol contribute to the suppression of FOXO3 and aggravation of liver damage. The results of the study are presented in The American Journal of Pathology: Hepatitis C and Alcohol Exacerbate Liver Injury by Suppression of FOXO3

A research team led by Dr. Steven A. Weinman gave alcohol to FOXO3-deficient mice for three weeks. A third of the animals in the liver tissues developed changes similar to those in alcoholic hepatitis in humans. Some of them had a tenfold increase in the level of alanine aminotransferase.

During the induction of alcoholic liver damage in a mouse model of viral hepatitis C, pronounced steatosis, focal inflammation and hydropic dystrophy of liver cells were observed. In animals, an increase in the level of alanine aminotransferase, an increase in the expression of ICAM-1 intercellular adhesion molecules, activation of caspase 3 and the release of FOXO3 from the cell nucleus into the cytosol were detected.

In cell culture, hepatitis C virus and alcohol separately led to an increase in FOXO3 activity by various activation mechanisms. At the same time, the combination of viral infection and ethanol intake led to the inhibition of FOXO3, partly associated with the induction of its exit from the nucleus and faster destruction, which was not observed under the influence of alcohol and hepatitis C virus separately.

Similar data on the properties of FOXO3 were obtained by another research group from the University of Kansas Medical Center, published in the same issue of the journal: Critical Role of FOXO3a in Alcohol-Induced Autophagy and Hepatotoxicity. During an experiment led by Dr. Wen-Xing Ding, it was found that FOXO3 helps fight acute alcohol intoxication by activating autophagy, a process of lysosomal degradation that leads to the destruction of damaged organelles. At the same time, in mice with FOXO3 deficiency, ethanol caused a decrease in the expression of genes responsible for autophagy and led to more severe liver damage.

According to the researchers, both the experiment with the induction of acute alcohol intoxication and the work of Dr. Weyman and colleagues on the model of chronic damage allowed us to confirm that FOXO3 helps a healthy liver to fight the hepatotoxic effect of ethanol.

The results of the conducted studies help to explain why only some people who drink alcohol develop a pronounced liver malfunction. Transcription factor FOXO3 is a protection factor against alcohol damage, which is disrupted when the harmful effects of alcohol-containing beverages are combined with hepatitis C virus infection. In this regard, scientists talk about the prospects for the treatment of combined alcohol-viral liver lesions by modulating the activity of FOXO3.

Portal "Eternal youth" http://vechnayamolodost.ru03.12.2013

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