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Potential role of heme metabolism in the inducible expression of heme oxygenase-1
- Source :
- Biochimica et Biophysica Acta (BBA) - General Subjects. 1861:1813-1824
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Background The degradation of heme significantly contributes to cytoprotective effects against oxidative stress and inflammation. The enzyme heme oxygenase-1 (HO-1), involved in the degradation of heme, forms carbon monoxide (CO), ferrous iron, and bilirubin in conjunction with biliverdin reductase, and is induced by various stimuli including oxidative stress and heavy metals. We examined the involvement of heme metabolism in the induction of HO-1 by the inducers sulforaphane and sodium arsenite. Methods We examined the expression of HO-1 in sulforaphane-, sodium arsenite- and CORM3-treated HEK293T cells, by measuring the transcriptional activity and levels of mRNA and protein. Results The blockade of heme biosynthesis by succinylacetone and N-methyl protoporphyrin, which are inhibitors of heme biosynthesis, markedly decreased the induction of HO-1. The knockdown of the first enzyme in the biosynthesis of heme, 5-aminolevulinic acid synthase, also decreased the induction of HO-1. The cessation of HO-1 induction occurred at the transcriptional and translational levels, and was mediated by the activation of the heme-binding transcriptional repressor Bach1 and translational factor HRI. CO appeared to improve the expression of HO-1 at the transcriptional and translational levels. Conclusions We demonstrated the importance of heme metabolism in the stress-inducible expression of HO-1, and also that heme and its degradation products are protective factors for self-defense responses. General significance The key role of heme metabolism in the stress-inducible expression of HO-1 may promote further studies on heme and its degradation products as protective factors of cellular stresses and iron homeostasis in specialized cells, organs, and whole animal systems.
- Subjects :
- 0301 basic medicine
Sodium arsenite
Arsenites
Bilirubin
Biophysics
Protoporphyrins
Heme
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Isothiocyanates
medicine
Humans
Molecular Biology
Carbon Monoxide
Chemistry
Biliverdin reductase
Sodium Compounds
Fanconi Anemia Complementation Group Proteins
Heptanoates
Heme oxygenase
Basic-Leucine Zipper Transcription Factors
HEK293 Cells
030104 developmental biology
Enzyme Induction
Sulfoxides
Protoporphyrin
Heme Oxygenase-1
Oxidative stress
HeLa Cells
Sulforaphane
Subjects
Details
- ISSN :
- 03044165
- Volume :
- 1861
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Accession number :
- edsair.doi.dedup.....14a23dc3d3b717c4ce3f2dd3876a1335