Potential involvement of oxygen intermediates and glutathione depletion in UV-induced epidermal cell injury in vitro

Conference · Mon Mar 11 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5906718

Hsieh, G C; Acosta, D ^[1]

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1. Univ. of Texas, Austin (United States)

Generation of reactive oxygen species (ROS) and depletion of glutathione (GSH) are suggested as the cytotoxic mechanisms for UVB-induced cellular damage. Primary monolayer cultures of epidermal keratinocytes (KCs) prepared from the skin of neonatal rats were irradiated with UVB at levels of 0.25-3.0 J/cm{sup 2}. Cytotoxicity was measured at 3, 6, and 12 hr after UVB radiation. Exposure of KCs to UVB resulted in time- and dose-related toxic responses as determined by plasma membrane integrity, lysosomal function and mitochondrial metabolic activity. Irradiated KCs generated superoxide in a dose-dependent manner when compared to sham-irradiated cells. Superoxide formation, which occurred before and concomitant with cell injury, was decreased by superoxide dismutase (SOD). Cell injury was also significantly prevented by ROS scavengers, SOD and catalase. Pretreatment of cells with endocytosis inhibitors, cytochalasin B and methylamine, suppressed the ability of SOD and catalase to protect keratinocytes from UVB-induced toxicity. Irradiation of cells with UVB caused rapid depletion of GSH to about 30% of unirradiated levels within 15 min. UVB-irradiation led to a rapid transient increase in GSH peroxidase activity, concomitant with a marked decrease in the GSH/GSSG ratio. After 1 hr., while the GSH/GSSG ratio remained low, the GSH peroxidase activity declined below the control levels in UVB-treated epidermal cells. Following extensive GSH depletion in cells preincubated with 0.1 mM buthiomine sulfoximine, KCs became strongly sensitized to the cytotoxic action of UVB. These results indicate that UVB-induced cell injury in cultured KCs may be mediated by ROs and that endogenous GSH may play an important protective role against the cytotoxic action of UVB.

• OSTI ID: 5906718
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL RADIATION EFFECTS
GLUTATHIONE
RADIOSENSITIVITY EFFECTS
CATALASE
CELL MEMBRANES
DOSE-RESPONSE RELATIONSHIPS
EPIDERMIS
IN VITRO
LYSOSOMES
MITOCHONDRIA
NEONATES
RATS
SUPEROXIDE DISMUTASE
TIME DEPENDENCE
ULTRAVIOLET RADIATION
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BODY
CELL CONSTITUENTS
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
EPITHELIUM
MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEPTIDES
PEROXIDASES
POLYPEPTIDES
PROTEINS
RADIATION EFFECTS
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RODENTS
SKIN
TISSUES
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture