Protein glutathionylation in human central nervous system: Potential role in redox regulation of neuronal defense against free radicals

Neuronal defense against free radicals is mediated primarily by the glutathione system. A cerebral defect of this system gives rise to the oxidative stress occurring in some neurological diseases. Glutathione provides a means of regulating protein function by glutathionylation, consisting of the formation of mixed disulfides between cysteines and glutathione. The glutathionylation of proteins, during both constitutive metabolism and oxidative stress, represents for the cell a mechanism to link physiological processes, and/or adaptive stress responses, to changes in intracellular redox states. In this study, we analyzed the topographic distribution of the protein glutathionylation normally occurring in human central nervous system. Constitutively glutathionylated proteins appeared uniformly distributed throughout all cortical layers of the cerebral and cerebellar cortex as well as throughout the gray matter of the spinal cord. The degree of immunocytochemical staining was clear in neurons, mild in oligodendrocytes, and weaker in astrocytes. The proteins preferentially glutathionylated were cytoskeletal proteins. Our results suggest a potential role of glutathionylation in the redox regulation of neuronal survival and in the control of axon/dendrite stability. (C) 2005 Wiley-Liss, Inc.