Lipid peroxidation scavengers prevent the carbonylation of cytoskeletal brain proteins induced by glutathione depletion.
In this study, we investigated the possible link between lipid peroxidation (LPO) and the formation of protein carbonyls (PCOs) during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH depletor diethyl maleate (DEM) in the absence or presence of classical LPO scavengers: trolox, caffeic acid phenethyl ester (CAPE), and butylated hydroxytoluene (BHT). All three scavengers reduced DEM-induced lipid oxidation and protein carbonylation, suggesting that intermediates/products of the LPO pathway such as lipid hydroperoxides, 4-hydroxynonenal and/or malondialdehyde are involved in the process. Additional in vitro experiments revealed that, among these products, lipid hydroperoxides are most likely responsible for protein oxidation. Interestingly, BHT prevented the carbonylation of cytoskeletal proteins but not that of soluble proteins, suggesting the existence of different mechanisms of PCO formation during GSH depletion. In pull-down experiments, beta-actin and alpha/beta-tubulin were identified as major carbonylation targets during GSH depletion, although other cytoskeletal proteins such as neurofilament proteins and glial fibrillary acidic protein were also carbonylated. These findings may be important in the context of neurological disorders that exhibit decreased GSH levels and increased protein carbonylation such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis.
Bizzozero
Oscar A
OA
Department of Cell Biology and Physiology, University of New Mexico-Health Sciences Center, Albuquerque, NM 87131-5218, USA. obizzozero@salud.unm.edu
Reyes
Savanna
S
Ziegler
Jennifer
J
Smerjac
Suzanne
S
D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000502:physiology*; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000187:drug effects*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000447:Aldehydes; D003598:Cytoskeletal Proteins; D016166:Free Radical Scavengers; D015289:Leukotrienes; D008054:Lipid Peroxides; D009419:Nerve Tissue Proteins; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D005978:Glutathione; C027576:4-hydroxy-2-nonenal