Thymic peptides increase glutathione level and glutathione disulfide reductase activity in vascular endothelial cells.
The glutathione redox cycle plays an important role in antioxidant and detoxification mechanisms. We recently reported that a calf thymic peptide (TP) protected vascular endothelial cells from oxidant injury induced by hydrogen peroxide. Using electrophoresis and amino acid sequencing analysis, we have now shown that TP consists of two peptides. The fast-moving peptide has 9 amino acid residues at the NH2 terminal and accounts for 92% of total quantity, while the other peptide has 18 amino acid residues at the NH2 terminal and amounts to 8%. The present study investigated the effect of TP on glutathione redox cycle. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were incubated with TP (12.5-100 micrograms/mL) for 24-48 h. TP caused a dose-dependent increase in glutathione (GSH) level and glutathione disulfide reductase activity but no significant change in GSH peroxidase activity. Exposure of PAEC to an organic oxidant t-butyl hydroperoxide (tBHP) resulted in decreased GSH level, increased lipid peroxidation, and elevated leakage of intracellular lactate dehydrogenase. Preincubation of PAEC with TP prevented these changes induced by tBHP. The data suggest that the antioxidant effect of TP may be due, at least in part, to its modulation of the GSH redox cycle in vascular endothelial cells. TP may thus be considered a new antioxidant with novel activities in addition to being an immune regulator.
Li
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Department of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, California 92350, USA.
Clark
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K
Lau
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BH
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005980:Glutathione Reductase / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010455:Peptides / Q000032:analysis / Q000502:physiology*; D010545:Peroxides / Q000494:pharmacology; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D013950:Thymus Gland / Q000502:physiology*; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D010455:Peptides; D010545:Peroxides; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase; D011490:Protein Disulfide Reductase (Glutathione); D005978:Glutathione; D019803:Glutathione Disulfide