Down-regulation of HCW9 mRNA in rat hepatocytes during chemical hypoxia involves both transcriptional and posttranscriptional mechanisms.
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.
Wang
H
H
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina at Chapel Hill 27599-7090, USA.
Harrison-Shostak
D C
DC
Lemasters
J J
JJ
Herman
B
B
D000818:Animals; D001483:Base Sequence; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000378:metabolism; D009928:Organ Specificity; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic
D017931:DNA Primers; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C055324:phospholipase A2-activating protein; D003609:Dactinomycin; D010741:Phospholipases A; D054467:Phospholipases A2