Down-regulation of HCW9 mRNA in rat hepatocytes during chemical hypoxia involves both transcriptional and posttranscriptional mechanisms

Abstract

HCW9 cDNA encodes a rat protein with 95% homology to mouse phospholipase A2 activating protein (PLAP). Its mRNA, which is substantially decreased in rat hepatocytes during chemical hypoxic injury, was found to be expressed in all rat tissues examined, including liver, heart, brain, spleen, lung, skeletal muscle, kidney, and testis. To elucidate the mechanisms responsible for this hypoxia-induced down-regulation of HCW9 mRNA levels, the transcription rate and half-life of HCW9 mRNA were measured. Nuclear run-off assays revealed a 54-57% inhibition in the transcription rate of HCW9 gene during chemical hypoxic injury. The half-life of HCW9 mRNA decreased from approximately 15 min under normoxic conditions to approximately 7 min during chemical hypoxic injury. These findings suggest that HCW9 expression in rat hepatocytes is regulated at both the transcriptional and posttranscriptional levels during chemical hypoxia.