Targeting Sod by Gene and Protein Engineering and Inhibition of Oxidative Stress in Various Diseases
A large number of human-type enzymes and bioactive peptides has been produced by gene engineering technique. Based on molecular mechanisms for various diseases, some patients have been treated successfully with such recombinant enzymes and peptide hormones without immunological complications and nonspecific side effects. However, recent studies revealed that there are many cases in which such recombinant products failed to show therapeutic effect predominantly due to their unfavorable in vivo behavior. It should be noted that enzymes and bioactive peptides could have their metabolic impact only when sufficient amounts of these molecules were localized in appropriate compartments during the time required for metabolic modulation. Thus, targeting enzymes and bioactive peptides to their appropriate sites of action is prerequisite to normalize pathologic metabolism in a patient.
KeywordsPlasma Half Life Bioactive Peptide Lethal Arrhythmia Reperfusion Arrhythmia Acute Gastric Mucosal Lesion
Unable to display preview. Download preview PDF.
- 1.P. Pyatak, A. Abuchowski, F. Davis, Preparation of polyethylene glycol: Superoxide adduct, and an examination of its blood circulating life and anti-inflammatory activity, Res. Commun. Chem. Pathol. Pharmacol., 29: 113-127 (1980).Google Scholar
- 2.C. Beauchamp, S. Gonias, D. Menapace, S. Pizzo, A new procedure for the synthesis of polyethylene glycol-protein adducts; Effects on function, receptor recognition, and clearance of Superoxide dismutase, lactoferrin, and 2-macroglobulin, Anal. Biochem., 131: 25–33 (1983).Google Scholar
- 3.M. Inoue, Metabolism and transport of amphipathic molecules in analbuminemic rats and human subjects, Hepatology, 5: 892–898 (1985).Google Scholar
- 4.M. Inoue, Albumin, a biovehicle for amphipathic molecules in the circulation, Seikagaku, 59: 441–447 (1987).Google Scholar
- 6.M. Inoue, N. Watanabe, Y. Morino, Synthesis of a Superoxide dismutase derivative that circulates bound to albumin and accumulates in a tissue whose pH is decreased, Biochemistry, 28: 6619–6624 (1989).Google Scholar
- 7.M. Inoue, M. Hirota, Y. Ando, T. Ogino, I. Ebashi, M. Akagi,Google Scholar
- Y. Morino, Role of oxygen radicals in the pathogenesis of acute gastric mucosal lesion, in: Free Radicals in Digestive Diseases, M. Tsuchiya, ed., pp83–98, Excerpta Medica, New York (1988)Google Scholar
- 8.N. Watanabe, M. Inoue, Y. Morino, Inhibition of postischemic reperfusion arrhythmias by an SOD derivative that circulates bound to albumin with prolonged in vivo half life, Biochem. pharmacol., in press (1989).Google Scholar
- 10.M. Inoue, N. Watanabe, Y. Tanaka, T. Amachi, J. Sasaki, Inhibition of oxidative tissue injury by targeting SOD to endothelial cell surface. Cell Struct. Funct. in press (1989).Google Scholar