Effects of dihydrolipoic acid on peptide methionine sulfoxide reductase. Implications for antioxidant drugs.
By showing that dihydrolipoic acid (DHLA) reactivates oxidatively damaged alpha-1 antiprotease (alpha 1-AP), a new antioxidant property of DHLA is described. For the first time, it is shown that a drug is able to reverse oxidative damage of physiologically essential macromolecules. Until now, only antioxidant properties have been reported that prevent oxidative stress. Repair of oxidized alpha 1-AP is catalysed by peptide methionine sulfoxide reductase (PMSR, EC 1.8.4.6). It is found that DHLA acts as a reducing cofactor for PMSR. Oxidized alpha 1-AP has been implicated in the etiology of certain lung diseases. Generally, by stimulating PMSR, DHLA may exert a curative effect in diseases accompanied by oxidative stress.
Biewenga
G P
GP
Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, Department of Pharmacochemistry, The Netherlands.
Veening-Griffioen
D H
DH
Nicastia
A J
AJ
Haenen
G R
GR
Bast
A
A
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002853:Chromatography, Liquid; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051150:Methionine Sulfoxide Reductases; D010088:Oxidoreductases / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019163:Reducing Agents / Q000737:chemistry; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000975:Antioxidants; D019163:Reducing Agents; D000515:alpha 1-Antitrypsin; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase