Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of inorganic metals and metalloporphyrins in the induction of mRNAs for haem oxygenase and heat-shock protein 70 (hsp70), the two heat-shock proteins, was examined in human HepG2 and Hep3B hepatoma cells. SnCl2, but not Sn-protoporphyrin, was found to be a potent inducer of both haem oxygenase and hsp70 mRNAs. In contrast, CoCl2, ZnCl2 and FeCl2 caused little induction of haem oxygenase and hsp70 mRNAs, whereas the porphyrin complexes of these metals strongly induced haem oxygenase mRNA, without influencing the level of hsp70 mRNA. The induction process was largely transcriptional, as judged by the inhibition of induction by actinomycin D, but not by cycloheximide, and by increased transcription demonstrated by nuclear run-off analysis. Since CoCl2 is a potent inducer of haem oxygenase in vivo in animals, the possibility of the biosynthesis of Co-protoporphyrin was examined in human hepatoma cells by incubating them with CoCl2 and protoporphyrin, or delta-aminolaevulinate (ALA), the precursor of protoporphyrin. Both types of treatment led to a potent induction of haem oxygenase mRNA. Co-protoporphyrin formation was also spectrally demonstrated in cells incubated with the metal and ALA. The results of this study indicate that certain metals, e.g. SnCl2, may directly induce haem oxygenase mRNA, whereas with other elements, incorporation of the metal into the porphyrin macrocycle is necessary for induction. Therefore CoCl2, like haemin, may activate the haem oxygenase gene via a haem-responsive transcription factor, whereas SnCl2 may exert its effect via a metal-responsive transcription factor.
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PMID:The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells. 838 46

Heme oxygenase (HO) activity oxidizes heme, releasing carbon monoxide; heme iron; and biliverdin, which is converted to bilirubin by biliverdin reductase. Inducible HO-I expression is a marker of oxidative stress in mammalian cells, while noninducible HO-II contributes to basal HO activity. HO-I and HO-II activities are implicated in cellular antioxidant defense mechanisms. We describe a microassay for HO activity in cultured human cells, using high-performance liquid chromatography of biliverdin and bilirubin. The assay is sufficiently sensitive to quantify basal and inducible HO activity in various human cell types. We have established human cell lines overexpressing heme oxygenase-II activity in microsomes using a metallothionein promoter-regulated expression system. Stable transformants treated with ZnCl2 express up to ninefold induction of HO activity. We have constructed human cell lines overexpressing HO-II protein and activity (5-15-fold) in the absence of tetracycline, using the HtTA-1 cell line transfected with tetracycline-regulated expression vectors (Gossen et al., Proc. Natl. Acad. Sci. USA 89, 1992). Functional HO-II overexpressing clones will be useful in investigating anti- or pro-oxidant effects of HO activity during cellular oxidative stress.
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PMID:A chromatographic assay for heme oxygenase activity in cultured human cells: application to artificial heme oxygenase overexpression. 960 6

Ondamtanggagambang (ODG) has been used as a prescription for psychological anxiety and depression in Korean medicine. In this study, we found that ODG have protective effects against oxidative stress in cardiomyocytes. Pretreatment with ODG extract prevented H2O2 and ZnCl2-induced cell damage in H9c2 cardiomyocytes, whereas simultaneous treatment of ODG extract did not. The protective effect of ODG extract on oxidative stress-induced damage was suppressed significantly by heme oxygenase (HO) inhibitors, zinc protoporphyrin-IX (ZnPP-IX, p < 0.01) and tin protoporphyrin-IX (SnPP-IX, p < 0.01) in H9c2 cells. ODG stimulation of cells strongly induced the expression of HO-1 protein. Taken together, it is suggested that ODG-induced expression of HO-1 may have a beneficial role in cardiomyocytes under oxidative stress.
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PMID:Protective effects of Korean herbal remedy against oxidative stress in cardiomyocytes. 1652 Nov 15