Thyroid status modulates glycoxidative and lipoxidative modification of tissue proteins.
Steady state protein modification by carbonyl compounds is related to the rate of carbonyl adduct formation and the half-life of the protein. Thyroid hormones are physiologic modulators of both tissue oxidative stress and protein degradation. The levels of the glycation product N(epsilon)-fructoselysine (FL) and those of the oxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and malondialdehyde-lysine (MDA-lys), identified by GC/MS in liver proteins, decreased significantly in hyperthyroid rats, as well as (less acutely) in hypothyroid animals. Immunoblotting of liver proteins for advanced glycation end-products (AGE) is in agreement with the results obtained by GC/MS. Cytosolic proteolytic activity against carboxymethylated foreign proteins measured in vitro was significantly increased in hypo- and hyperthyroidism. Oxidative damage to DNA, estimated as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG), did not show significant differences between groups. The results suggests that the steady state levels of these markers depend on the levels of thyroid hormones, presumably through their combined effects on the rates of protein degradation and oxidative stress, whereas DNA is more protected from oxidative damage.
Pamplona
R
R
Metabolic Physiopathology Research Group, Department of Basic Medical Sciences, Faculty of Medicine, University of Lleida, Spain. manuel.portero@cmb.udl.es
Portero-Otín
M
M
Ruiz
C
C
Bellmunt
M J
MJ
Requena
J R
JR
Thorpe
S R
SR
Baynes
J W
JW
Romero
M
M
López-Torres
M
M
Barja
G
G
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D010450:Endopeptidases / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000097:blood
D015415:Biomarkers; D005227:Fatty Acids; D017127:Glycation End Products, Advanced; D013963:Thyroid Hormones; C033186:fructosyl-lysine; D008315:Malondialdehyde; C048496:N(6)-carboxymethyllysine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010450:Endopeptidases; D003849:Deoxyguanosine; D008239:Lysine