Studies of the role of selenium-independent and selenium-dependent glutathione peroxidases in eicosanoid biosynthesis

Thesis/Dissertation · Mon Jan 01 04:00:00 EST 1990

OSTI ID:6968243

Zisman, A H

Glutathione S-transferases are involved in the biotransformation and/or detoxification of a wide range of organic compounds, including allylic epoxides. GSTs catalyze the transformation of prostaglandin (PG)H[sub 2] into PGE[sub 2] and/or PGF[sub 2alpha]. Specific GST isozymes possessing non-selenium glutathione-peroxidase activity (NonSe-GSH-PX) catalyze the direct reduction of PGH[sub 2] to PGF[sub 2alpha]. Other GST isozymes have been reported to catalyze the transformation of leukotriene (LT)A[sub 4] into LTC[sub 4]. In this study, human liver GSTs were purified and individual isozymes were characterized by SDS electrophoresis, isoelectric focusing, substrate specificities, immunological cross reactivities, and their ability to catalyze the transformation of PGH[sub 2] to PGF[sub 2alpha], and LTA[sub 4] to LTC[sub 4]. The GST isozyme expression pattern in man varies between individuals. Se-dependent GSH-PX activity (Se-GSH-PX) also plays a role in eicosanoid metabolism. The author infused Se-adequate and Se-deficient dairy cattle with endotoxin into the mammary gland to simulate an inflammation. Arachidonic acid metabolites were extracted and analyzed in both the milk and the milk polymorphonuclear leukocytes (PMNs). PMN's cytosol was assayed for Se- and nonSe-GSH-PX, and GST activity. The results indicate that the Se-deficient cows had lower levels (p < 0.05) of PGE[sub 2] and TXB[sub 2] released into the milk following challenge; however, there was no significant effect on the arachidonic acid metabolites produced by the milk PMNs. Although the Se-deficient cows had significantly lower levels (p < 0.05) of Se-GSH-PX activity, there was no effect on the GST nor NonSe-GSH-PX activity. Overall, eicosanoid biosynthesis is complex, being influenced by both dietary and enzymatic manipulation. The data support Se- and nonSe-GSH-PX playing important roles in eicosanoid formation.

• Research Organization: Pennsylvania State Univ., University Park, PA (United States)
• OSTI ID: 6968243
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism &amp; Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTIGENS
ARACHIDONIC ACID
BIOASSAY
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CATTLE
CHEMICAL REACTIONS
COWS
DETOXIFICATION
DIGESTIVE SYSTEM
DOMESTIC ANIMALS
DRUGS
EICOSANOIC ACID
ELECTROPHORESIS
ELEMENTS
ENDOTOXINS
ENZYMES
EPOXIDES
GLANDS
GLUTATHIONE
HAZARDOUS MATERIALS
IMMUNOASSAY
ISOMERIZATION
LEUKOCYTES
LIVER
MAMMALS
MAN
MATERIALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEPTIDES
PEROXIDASES
POLYPEPTIDES
PRIMATES
PROSTAGLANDINS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RUMINANTS
SELENIUM
SEMIMETALS
SYNTHESIS
TOXIC MATERIALS
TOXINS
VERTEBRATES