Possible implications of the induction of human heme oxygenase-1 by nitric oxide donors.
To explore the involvement of nitric oxide (NO) in the induction of heme oxygenase-1, an essential enzyme in heme catabolism, we studied the effects of NO donors on the expression of heme oxygenase-1 mRNA in HeLa human cervical cancer cells. Treatment with each of three NO donors, sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-L-glutathione, caused noticeable increases in the expression levels of heme oxygenase- mRNA, but not heme oxygenase-2 mRNA. On the other hand, nitrite or 8-bromo cGMP exerted no noticeable effect on the levels of heme oxygenase-1 mRNA. We showed that sodium nitroprusside also increased the levels of heme oxygenase-1 protein. The sodium nitroprusside-mediated increase in heme oxygenase-1 mRNA levels was abolished by treatment with actinomycin D. The expression levels of heme oxygenase-1 mRNA were also increased by NO donors in human melanoma and neuroblastoma cell lines. Thus, the observed induction of heme oxygenase-1 may represent an important response to NO or NO-related oxidative stress. The half lives of heme oxygenase-1 and heme oxygenase-2 mRNAs were estimated to be about 3.2 h and more than 5 h, respectively.
Takahashi
K
K
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi.
Hara
E
E
Ogawa
K
K
Kimura
D
D
Fujita
H
H
Shibahara
S
S
D019070:Cell Lineage; D004790:Enzyme Induction; D006367:HeLa Cells; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D009569:Nitric Oxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2