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Title: Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance

Abstract

Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from <10 min to 40 h, reduced immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, the authors hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with /sup 125/I-PEG-catalase or /sup 125/I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Univ. of Alabama, Birmingham (USA)
OSTI Identifier:
6771901
Resource Type:
Journal Article
Journal Name:
J. Biol. Chem.; (United States)
Additional Journal Information:
Journal Volume: 263:14
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CATALASE; BIOCHEMISTRY; ENDOTHELIUM; ENZYME ACTIVITY; SUPEROXIDE DISMUTASE; CHROMIUM 51; ELECTRON SPIN RESONANCE; IODINE 125; LABELLED COMPOUNDS; OXIDOREDUCTASES; POLYETHYLENE GLYCOLS; XANTHINES; ALCOHOLS; ANIMAL TISSUES; AROMATICS; AZAARENES; BETA DECAY RADIOISOTOPES; BODY; CHEMISTRY; CHROMIUM ISOTOPES; DAYS LIVING RADIOISOTOPES; ELECTRON CAPTURE RADIOISOTOPES; ENZYMES; EVEN-ODD NUCLEI; GLYCOLS; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; MAGNETIC RESONANCE; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANIC POLYMERS; PEROXIDASES; POLYMERS; PURINES; RADIOISOTOPES; RESONANCE; TISSUES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Beckman, J S, Minor, Jr, R L, White, C W, Repine, J E, Rosen, G M, and Freeman, B A. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance. United States: N. p., 1988. Web.
Beckman, J S, Minor, Jr, R L, White, C W, Repine, J E, Rosen, G M, & Freeman, B A. Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance. United States.
Beckman, J S, Minor, Jr, R L, White, C W, Repine, J E, Rosen, G M, and Freeman, B A. 1988. "Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance". United States.
@article{osti_6771901,
title = {Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance},
author = {Beckman, J S and Minor, Jr, R L and White, C W and Repine, J E and Rosen, G M and Freeman, B A},
abstractNote = {Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from <10 min to 40 h, reduced immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, the authors hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with /sup 125/I-PEG-catalase or /sup 125/I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.},
doi = {},
url = {https://www.osti.gov/biblio/6771901}, journal = {J. Biol. Chem.; (United States)},
number = ,
volume = 263:14,
place = {United States},
year = {Sun May 15 00:00:00 EDT 1988},
month = {Sun May 15 00:00:00 EDT 1988}
}