Redox modulation of heat shock protein expression by acetylcarnitine in aging brain: relationship to antioxidant status and mitochondrial function.
Calabrese V, Colombrita C, Sultana R, Scapagnini G, Calvani M, Butterfield DA, Stella AM.
Section of Biochemistry and Molecular Biology, Department of Chemistry, Faculty of Medicine, University of Catania, Catania, Italy.
There is significant evidence to show that aging is characterized by a stochastic accumulation of molecular damage and by a progressive failure of maintenance and repair processes. Protective mechanisms exist in the brain which are controlled by vitagenes and include members of the heat shock system, heme oxygenase-I, and Hsp70 as critical determinants of brain stress tolerance. Given the broad cytoprotective properties of the heat shock response, molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Acetyl-L-carnitine is proposed as a therapeutic agent for several neurodegenerative disorders, and the present study reports that treatment for 4 months of senescent rats with acetyl-L-carnitine induces heme oxygenase-1 as well as Hsp70 and SOD-2. This effect was associated with upregulation of GSH levels, prevention of age-related changes in mitochondrial respiratory chain complex expression, and decrease in protein carbonyls and HNE formation. We hypothesize that maintenance or recovery of the activity of vitagenes may delay the aging process and decrease the risk of age-related diseases. Particularly, modulation of endogenous cellular defense mechanisms via acetyl-L-carnitine may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration.
PMID: 16677087 [PubMed - in process]
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Proteomics analyses of specific protein oxidation and protein expression in aged rat brain and its modulation by L-acetylcarnitine: insights into the mechanisms of action of this proposed therapeutic agent for CNS disorders associated with oxidative stress.
Poon HF, Calabrese V, Calvani M, Butterfield DA.
Department of Chemistry, University of Kentucky, Lexington, Kentucky.
Impaired function of the central nervous system (CNS) in aged animals is associated with increased susceptibility to the development of many neurodegenerative diseases. Age-related functional deterioration in brain is consistent with the free radical theory of aging that predicts, among other things, that free radical reactions with and damage to biomolecules, such as proteins and membrane lipid bilayers, leads to loss of neurons and subsequently diminished cognition. These oxidatively modified biomolecules are believed to contribute to the decreased antioxidant content, mitochondrial dysfunction, and impaired plasticity in aged brains. Treatment of rodents with L-acetylcarnitine (LAC; gamma-trimethyl-beta-acetylbutyrobetaine) can improve these functional losses. Although it is well established that administration of LAC can decrease protein oxidation in aged brains, it is not clear which proteins are decreased in their level of oxidation in the brains of aged rats treated with LAC. The current study used a parallel redox proteomics approach to identify the proteins that are oxidized in aged rat cortex and hippocampus of aged rats. Moreover, those proteins that are reduced in oxidation status were identified in aged brains from rats treated in vivo with LAC. The findings are discussed in reference to brain aging and age-related cognitive impairment.
PMID: 16677085 [PubMed - in process]