Rat mitochondrial ATP synthase ATP5G3: cloning and upregulation in pancreas after chronic ethanol feeding

Individuals with chronic excessive alcohol ingestion are put at the risk of acute and chronic pancreatitis. Underlying molecular mechanisms are unknow n. Differential gene expression in the pancreas was profiled using mRNA dif ferential display by comparison between control and ethanol-consuming rats. Male Wistar rats were fed with diets containing 6.7% (vol/vol) ethanol for 4 wk. A cDNA tag that was overexpressed in the pancreas of rats fed ethano l was isolated. A 723-bp cDNA was cloned from a rat pancreatic cDNA library , which encodes a novel rat mitochondrial ATP synthase subunit 9, isoform 3 (ATP5G3), which is homologous to a human ATP5G3 gene. Real-time PCR demons trated that all three nuclear gene isoforms (ATP5G1, ATP5G2, and ATP5G3) we re consistently upregulated in the pancreas of alcohol-consuming rats, para llel with mitochondrial injury. The cellular response to mitochondrial dama ge and metabolic stress may reflect an adaptive process for mitochondrial r epair in pancreatic acinar cells during chronic ethanol ingestion.