Induction of heme-binding protein 23/peroxiredoxin I gene expression by okadaic acid in cultured rat hepatocytes.
Heme-binding protein 23 (HBP23), also termed peroxiredoxin I (Prx I), is an antioxidant protein that is induced by various oxidative stress stimuli. HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity. To investigate the regulatory role of cellular phosphorylation and dephosphorylation events on hepatic HBP23/Prx I gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA) which is a specific inhibitor of the serine threonine protein phosphatases 1 and 2A. In hepatocyte cultures HBP23/Prx I was highly expressed for up to 5 days and, both protein and mRNA levels of HBP23/Prx I were induced by OA. The time kinetics of OA-dependent HBP23/Prx I mRNA upregulation were coordinate to that of heme oxygenase (HO)-1, which is the inducible isoform of the rate-limiting enzyme of heme-degradation. In contrast to HO-1, however, induction of HBP23/Prx I mRNA by OA was downregulated by dibutyryl-cAMP, and was enhanced by the specific protein kinase A inhibitors KT5720 and H-89. HBP23/Prx I induction by OA occurred on the transcriptional level as determined by studies with actinomycin D and nuclear run-off assays.
Immenschuh
Stephan
S
Institut für Klinische Chemie und Pathobiochemie der Justus-Liebig-Universität Giessen, 35392 Giessen, Germany. Stephan.Immenschuh@klinchemie.med.uni-giessen.de
Iwahara
Shin-Ichiro
S
Schwennen
Bianca
B
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019319:Okadaic Acid / Q000494:pharmacology*; D010544:Peroxidases / Q000096:biosynthesis* / Q000235:genetics; D054464:Peroxiredoxins; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D019319:Okadaic Acid; D010544:Peroxidases; D054464:Peroxiredoxins