Proteolysis of Oxidized Proteins after Oxygen–Glucose Deprivation in Rat Cortical Neurons is Mediated by the Proteasome
- 1 September 2001
- journal article
- research article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 21 (9), 1090-1096
- https://doi.org/10.1097/00004647-200109000-00006
Abstract
Oxidative injury contributes to cellular damage during and after cerebral ischemia. However, the downstream catabolic pathways of damaged cellular components in neurons are largely unknown. In the current study, the authors examined the formation of oxidized proteins and their active degradation by the proteasome. In near-pure rat primary cortical neurons, it was found that protein-bound carbonyls as markers for oxidized proteins are increased after oxygen-glucose deprivation (OGD). During and after OGD, degradation of proteins metabolically radiolabeled before OGD increases two-to threefold compared with the normal protein turnover. Proteolysis after reoxygenation was attenuated by the presence of dimethylthiourea, a radical scavenger, and was blocked by lactacystin, a specific proteasome inhibitor. Lactacystin also increased the amount of protein carbonyls formed. In contrast, the activity of the proteasome complex itself after OGD was not different from sham-washed controls. The authors suggest that oxygen-glucose deprivation increases free radicals, which, in turn, oxidize proteins that are recognized and actively degraded by the proteasome complex. This protease itself is relatively resistant against oxidative injury. The authors conclude that the proteasome may be an active part of the cellular defense system against oxidative stress after cerebral ischemia.Keywords
This publication has 28 references indexed in Scilit:
- Proteasome Inhibitor PS519 Reduces Infarction and Attenuates Leukocyte Infiltration in a Rat Model of Focal Cerebral IschemiaStroke, 2000
- Stable markers of oxidant damage to proteins and their application in the study of human diseaseFree Radical Biology & Medicine, 1999
- 4-Hydroxy-2-nonenal-mediated Impairment of Intracellular Proteolysis during Oxidative StressJournal of Biological Chemistry, 1999
- Protection from oxidative inactivation of the 20S proteasome byheat-shock protein 90Biochemical Journal, 1998
- Protein Carbonyl Measurement by a Sensitive ELISA MethodFree Radical Biology & Medicine, 1997
- Degradation of Oxidized Proteins in K562 Human Hematopoietic Cells by ProteasomeJournal of Biological Chemistry, 1996
- Role of Oxidants in Ischemic Brain DamageStroke, 1996
- Structural alterations in synaptosomal membrane-associated proteins and lipids by transient middle cerebral artery occlusion in the catNeurochemical Research, 1995
- Proteolysis in Cultured Liver Epithelial Cells during Oxidative StressJournal of Biological Chemistry, 1995
- Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assayJournal of Neuroscience Methods, 1987