Oxidative modification of rat liver 5'-nucleotidase: the mechanisms for protection and re-activation.
The effect of oxidative stress catalysed by transition metals appears to have a critical relevance for the structure and function not only of membrane lipids but also of integral membrane proteins in a complex lipid-protein assembling, and membrane-dependent function. The integral membrane enzyme 5'-nucleotidase is susceptible to Fe((2+))-ion catalysed oxidative modification, and the extent of enzyme inhibition is in inverse relationship (r = -0.820) with lipid peroxidation (MDA) level. This work is also a comparative study about possible effectiveness of different Fe-ion chelators (deferoxamine, Na-citrate, Na-salicylate, ammonium oxalate and EDTA), antioxidants (GSH, GSH/GSH-Px system, Cu, Zn-SOD and mannitol) and metal cations (Mg(2+) and Mn(2+)) to protect or restore Fe(2+)-ion induced 5'-nucleotidase inhibition and to suppress Fe(2+)-ion enhanced lipid peroxidation. Among the examined chelators it was only deferoxamine and Na-citrate that exerted a fully protective and reactivating ability; among the antioxidants it was only GSH; among the metal cations it was only Mn(2+). The ability to protect or restore 5'-nucleotidase activity and to diminish chain-induced lipid peroxidation is explicable in terms of: metal-binding ability, capacity of taking iron away from a biological molecule, or ability of transferring the damage to itself. After a short incubation period, the iron associated with enzyme or lipid hydroperoxides could be in a labile coordinative linkage, still able to interact with possible ligands or metal cations.
Kocic
G
G
Institute for Biochemistry, School of Medicine, University of Nis, Yukoslavia. kocicrg@bankerinter.net
Pavlovic
D
D
Jevtovic
T
T
Kocic
R
R
Bojic
A
A
Vlahovic
P
P
Djordjevic
V
V
Sokolovic
D
D
Djindjic
B
B
D015720:5'-Nucleotidase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002614:Chelating Agents / Q000378:metabolism; D004789:Enzyme Activation; D005296:Ferrous Compounds / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007978:Levamisole / Q000494:pharmacology; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology*; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats
D000975:Antioxidants; D002614:Chelating Agents; D005296:Ferrous Compounds; D007978:Levamisole; D008315:Malondialdehyde; D015720:5'-Nucleotidase