Receptor-mediated transport of heme by hemopexin regulates gene expression in mammalian cells.
Hemopexin (HPX) transports heme to liver parenchymal cells, undergoes receptor-mediated endocytosis, and recycles intact. Incubation of mouse hepatoma (Hepa) cells with heme-HPX causes a rapid dose- and time-dependent increase in the steady-state level of heme oxygenase (HO) mRNA. A maximum induction of 20-25-fold is achieved within 3 h after incubation with 10 microM heme-HPX. This accumulation of HO mRNA results primarily from increased transcription of the HO gene as judged by in vitro nuclear run-on assays. In addition, receptor-mediated transport of heme into Hepa cells significantly decreases the steady-state level of transferrin receptor (TfR) mRNA. While a 25-30-fold decrease in the amount of TfR mRNA is observed within 3 h of incubation of Hepa cells with 10 microM heme-HPX, no significant change in the rate of TfR gene transcription was detected. These regulatory effects of heme-HPX are not restricted to hepatic cells but are also observed in human promyelocytic HL-60 cells. This is the first direct demonstration of receptor-mediated transport of heme by hemopexin regulating gene expression in mammalian cells.
Alam
J
J
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112.
Smith
A
A
D000818:Animals; D002460:Cell Line; D004705:Endocytosis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005796:Genes / Q000187:drug effects; D006418:Heme / Q000378:metabolism*; D006466:Hemopexin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C028027:heme receptor; D006418:Heme; D006466:Hemopexin