Induction of heme oxygenase: A general response to oxidant stress in cultured mammalian cells
- Swiss Institute for Experimental Cancer Research, Epalinges (Switzerland)
Accumulation of heme oxygenase mRNA is strongly stimulated by treatment of cultured human skin fibroblasts with ultraviolet radiation, hydrogen peroxide, or the sulfhydryl reagent sodium arsenite. Since this will result in a transient reduction in the prooxidant state of cells, the phenomenon may represent an important inducible antioxidant defense mechanism. To examine the generality of the response, we have measured the accumulation of the specific mRNA in a variety of human and mammalian cell types after inducing treatments. Induction by sodium arsenite is observed in all additional human cell types tested. This includes primary epidermal keratinocytes and lung and colon fibroblasts as well as established cell lines such as HeLa, TK6 lymphoblastoid, and transformed fetal keratinocytes. Strong induction of heme oxygenase mRNA is also observed following sodium arsenite treatment of cell lines of rat, hamster, mouse, monkey, and marsupial origin. The agents which lead to induction in cultured human skin fibroblasts fall into two categories: (a) those which are oxidants or can generate active intermediates (ultraviolet A radiation, hydrogen peroxide, menadione, and the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate); (b) agents which are known to interact with or modify cellular glutathione levels (buthionine sulfoximine, sodium arsenite, iodoacetamide, diamide, and cadmium chloride). These observations strongly support the hypothesis that induction of the enzyme is a general response to oxidant stress in mammalian cells and are consistent with the possibility that the cellular redox state plays a key role.
- OSTI ID:
- 6056999
- Journal Information:
- Cancer Research; (USA), Vol. 51:3; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
BIOLOGICAL ADAPTATION
HYDROGEN PEROXIDE
BIOLOGICAL EFFECTS
OXYGENASES
ENZYME INDUCTION
PHORBOL ESTERS
REAGENTS
DOSE-RESPONSE RELATIONSHIPS
MAN
MESSENGER-RNA
SKIN
ULTRAVIOLET RADIATION
ANIMAL CELLS
ANIMALS
BODY
CARCINOGENS
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
ENZYMES
ESTERS
GENE REGULATION
HYDROGEN COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
PRIMATES
RADIATIONS
RNA
SOMATIC CELLS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 - Chemicals Metabolism & Toxicology
550200 - Biochemistry