Mechanism of induction of heme oxygenase by metalloporphyrins in primary chick embryo liver cells: evidence against a stress-mediated response.
Heme oxygenase catalyzes the first and rate-controlling step in heme catabolism. One of the two forms of heme oxygenase (heme oxygenase-1) has been shown to be increased by heme, metals, and in some systems, by certain environmental stresses. However, it remains uncertain whether heme induces hepatic heme oxygenase-1 by a general stress response, or a specific heme-dependent cellular response. The work communicated here explores this issue by examining possible mechanisms whereby heme and other metalloporphyrins induce heme oxygenase-1 in normal liver cells. Primary cultures of chick embryo liver cells were tested for their ability to increase heme oxygenase mRNA after exposure to selected metalloporphyrins (heme, chromium mesoporphyrin, cobalt protoporphyrin and manganese protoporphyrin). The ability of antioxidants to decrease metalloporphyrin-mediated induction of heme oxygenase-1 mRNA was also tested. Our results indicate that: 1) the increase in heme oxygenase-1 mRNA mediated by heme or other metalloporphyrins may involve a short-lived protein(s) since the increase was prevented by several inhibitors of protein synthesis; and 2) in normal liver cells, heme-dependent oxidative stress does not play a key role in the heme-mediated induction of heme oxygenase-1. We conclude that heme and other non-heme metalloporphyrins induce heme oxygenase-1 through a mechanism requiring protein synthesis, not because metalloporphyrins increase cellular oxidative or other stress.
Cable
E E
EE
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
Gildemeister
O S
OS
Pepe
J A
JA
Lambrecht
R W
RW
Bonkovsky
H L
HL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002642:Chick Embryo; D005786:Gene Expression Regulation; D006418:Heme / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism
D000975:Antioxidants; D008665:Metalloporphyrins; D012333:RNA, Messenger; D006418:Heme; D006419:Heme Oxygenase (Decyclizing)