TY - JOUR

T1 - γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde

T2 - Biomarkers of oxidative damage to proteins

AU - Daneshvar, B

AU - Frandsen, H

AU - Autrup, H.

AU - Dragsted, Lars Ove

N1 - (Ekstern)

PY - 1997

Y1 - 1997

N2 - Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify oxidized amino acids in blood proteins which might serve as biomarkers of oxidative damage. When oxidative damage is induced into bovine serum albumin by metal-catalysed oxidation systems, the aldehyde groups formed can be derivatized by fluoresceinamine (FINH2). Following acid hydrolysis of FINH2-derivatized protein, two major oxidation products, γ-glutamyl semialdehyde (GGS) and 2-amino-adipic semialdehyde (AAS), were found and identified by HPLC and MS. Isolation and identification of oxidized amino acids from homopolymers (poly-Arg, -Pro, -Lys, -Trp or -Leu) confirmed that GGS can originate from Arg or Pro, while AAS is an oxidation product of Lys. When oxidative stress was induced in rats by treatments with t-butyl hydroperoxide or acrolein, rat plasma protein levels of GGS and AAS were found to be significantly higher compared with control rats. The AAS-content in serum albumin or in total plasma proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found for both GGS and AAS. We conclude that GGS or AAS may be useful novel biomarkers of oxidative damage to proteins in vivo.

AB - Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify oxidized amino acids in blood proteins which might serve as biomarkers of oxidative damage. When oxidative damage is induced into bovine serum albumin by metal-catalysed oxidation systems, the aldehyde groups formed can be derivatized by fluoresceinamine (FINH2). Following acid hydrolysis of FINH2-derivatized protein, two major oxidation products, γ-glutamyl semialdehyde (GGS) and 2-amino-adipic semialdehyde (AAS), were found and identified by HPLC and MS. Isolation and identification of oxidized amino acids from homopolymers (poly-Arg, -Pro, -Lys, -Trp or -Leu) confirmed that GGS can originate from Arg or Pro, while AAS is an oxidation product of Lys. When oxidative stress was induced in rats by treatments with t-butyl hydroperoxide or acrolein, rat plasma protein levels of GGS and AAS were found to be significantly higher compared with control rats. The AAS-content in serum albumin or in total plasma proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found for both GGS and AAS. We conclude that GGS or AAS may be useful novel biomarkers of oxidative damage to proteins in vivo.

KW - Amino acid

KW - Carbonyl induction

KW - Protein oxidation

UR - http://www.scopus.com/inward/record.url?scp=0000461347&partnerID=8YFLogxK

U2 - 10.1080/135475097231841

DO - 10.1080/135475097231841

M3 - Journal article

AN - SCOPUS:0000461347

VL - 2

SP - 117

EP - 123

JO - Biomarkers

JF - Biomarkers

SN - 1354-750X

IS - 2

ER -