Role of glutathione in protecting endothelial cells (EC) against H/sub 2/O/sub 2/ oxidant injury
To determine the mechanism responsible for enhanced susceptibility of EC to oxidant injury in the absence of glucose, the authors determined EC injury (by /sup 3/HDOG release) in the presence of various oxygen radical scavengers (S) and they measured EC levels of glutathione following oxidant injury in the presence and absence of glucose. EC were damaged with oxygen radicals generated by phorbol myristate acetate (PMA) activated polymorphonuclear leukocytes (PMN) (90 minutes) or xanthine-xanthine oxidase (X-XO) (60 minutes) in the presence and absence of glucose and catalase (S of H/sub 2/O/sub 2/), superoxide dismutase (S of O/sub 2/-), isoleucine, valine, and serine (S of HOCl), or mannitol, ethanol, benzoic acid, dimethylsulfoxide and dimethylthiourea (S of OH/sup -/). In each oxygen radical generating system, in the presence and absence of glucose, only catalase significantly protected the EC from oxidant injury (P < 0.001). In the presence of glucose, EC glutathione levels were 10.3 +/- 4.7 nmoles/mg protein following a one hour exposure to 0.08 units/ml XO compared to 8.2 +/- 3.3 nmoles/mg protein in control EC (NS). In the absence of glucose EC glutathione levels decreased significantly (P < 0.01) to 4.3 +/- 1.3 nmoles/mg protein after a one hour exposure to 0.004 units/ml XO compared to 8.7 +/- 3.1 nmoles/mg protein in control EC. The authors conclude that H/sub 2/O/sub 2/ is the oxygen radical responsible for EC damage and that oxidant injury in the absence of glucose resulted in enhanced EC injury due to depletion of glutathione stores important in detoxifying H/sub 2/O/sub 2/.
- Research Organization:
- I.U.M.C., Indianapolis, IN
- OSTI ID:
- 5447703
- Report Number(s):
- CONF-8604222-; TRN: 86-028556
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ENDOTHELIUM
INJURIES
GLUTATHIONE
BIOLOGICAL EFFECTS
HYDROGEN PEROXIDE
TOXICITY
BENZOIC ACID
CATALASE
DMSO
ETHANOL
GLUCOSE
LEUCINE
OXIDOREDUCTASES
PHORBOL ESTERS
SERINE
SUPEROXIDE DISMUTASE
VALINE
ALCOHOLS
ALDEHYDES
AMINO ACIDS
ANIMAL TISSUES
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CARCINOGENS
DRUGS
ENZYMES
ESTERS
HEXOSES
HYDROGEN COMPOUNDS
HYDROXY ACIDS
HYDROXY COMPOUNDS
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDASES
PEROXIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
SACCHARIDES
SULFOXIDES
TISSUES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550201 - Biochemistry- Tracer Techniques