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Isabelle Petropoulos

Publications and source records attributed to Isabelle Petropoulos.

9 recordsLinked to original sources
PubMed2006

Alterations in mitochondrial and cytosolic methionine sulfoxide reductase activity during cardiac ischemia and reperfusion.

During cardiac ischemia/reperfusion, proteins are targets of reactive oxygen species produced by the mitochondrial respiratory chain resulting in the accumulation of oxidatively modified protein. Sulfur-containing amino acids are among the most sensitive to oxidation. Certain cysteine and methionine oxidation products can be reversed back to their reduced form within proteins by specific repair enzymes. Oxidation of methionine in protein produces methionine-S-sulfoxide and methionine-R-sulfoxide that can be catalytically reduced by two stereospecific enzymes, methionine sulfoxide reductases A and B, respectively. Due to the importance of the methionine sulfoxide reductase system in the maintenance of protein structure and function during conditions of oxidative stress, the fate of this system during ischemia/reperfusion was investigated. Mitochondrial and cytosolic methionine sulfoxide reductase activities are decreased during ischemia and at early times of reperfusion, respectively. Partial recovery of enzyme activity was observed upon extended periods of reperfusion. Evidence indicates that loss in activity is not due to a decrease in the level of MsrA but may involve structural modification of the enzyme.

Animals↗
PubMed2006

Maintenance of proteins and aging: the role of oxidized protein repair.

According to the free radical theory of aging proposed by Denham Harman (Journal of Gerontology 1956, 11, pp. 298-300), the continuous oxidative damage to cellular components over an organism's life span is a causal factor of the aging process. The age-related build-up of oxidized protein is therefore resulting from increased protein oxidative damage and/or decreased elimination of oxidized proteins. In this mini-review, we will address the fate, during aging, of the protein maintenance systems that are involved in the degradation of irreversibly oxidized proteins and in the repair of reversible protein oxidative damage with a special focus on the methionine sulfoxide reductases system. Since these protein degradation and repair systems have been found to be impaired with age, it is proposed that not only failure of redox homeostasis but, as importantly, failure of protein maintenance are critical factors in the aging process.

Aging↗
PubMed2006

Methionine sulfoxide reductases: relevance to aging and protection against oxidative stress.

Proteins are subject to modification by reactive oxygen species (ROS), and oxidation of specific amino acid residues can impair their biological function, leading to an alteration in cellular homeostasis. Methionine is among the amino acids the most susceptible to oxidation by almost all forms of ROS, resulting in both S and R diasteroisomeric forms of methionine sulfoxide. These modifications can be repaired specifically by the peptide methionine sulfoxide reductase A and B enzymes (MsrA and MsrB), respectively. MsrA has been detected in several organisms going from prokaryotes to eukaryotes. MsrA is tightly implicated in protection against oxidative stress and in protein maintenance, which is critical in the aging process. Several studies have shown that overexpression of MsrA led to an increased resistance against oxidative stress, while MsrA null mutants are more sensitive toward oxidative stress. Since oxidative damage is a key factor in aging, overexpression of MsrA in some organisms led to an increased life span whereas deletion of the gene led to the opposite. MsrA could also be involved, by regulating the function and/or expression of target proteins, in ROS-mediated signal transduction. In fact, changes in gene expression, including certain oxidative stress-response genes, have been observed when MsrA is overexpressed. This review elaborates on the current knowledge in the implication of the Msr system in protection against oxidative stress and aging.

Aging↗
PubMed2005

Overexpression of MsrA protects WI-38 SV40 human fibroblasts against H2O2-mediated oxidative stress.

Proteins are modified by reactive oxygen species, and oxidation of specific amino acid residues can impair their biological functions, leading to an alteration in cellular homeostasis. Oxidized proteins can be eliminated through either degradation or repair. Repair is limited to the reversion of a few modifications such as the reduction of methionine oxidation by the methionine sulfoxide reductase (Msr) system. However, accumulation of oxidized proteins occurs during aging, replicative senescence, or neurological disorders or after an oxidative stress, while Msr activity is impaired. In order to more precisely analyze the relationship between oxidative stress, protein oxidative damage, and MsrA, we stably overexpressed MsrA full-length cDNA in SV40 T antigen-immortalized WI-38 human fibroblasts. We report here that MsrA-overexpressing cells are more resistant than control cells to hydrogen peroxide-induced oxidative stress, but not to ultraviolet A irradiation. This MsrA-mediated resistance is accompanied by a decrease in intracellular reactive oxygen species and is partially abolished when cells are cultivated at suboptimal concentration of methionine. These results indicate that MsrA may play an important role in cellular defenses against oxidative stress, by catalytic removal of oxidant through the reduction of methionine sulfoxide, and in protection against death by limiting, at least in part, the accumulation of oxidative damage to proteins.

Aging↗
PubMed2005

Protein maintenance in aging and replicative senescence: a role for the peptide methionine sulfoxide reductases.

Cellular aging is characterized by the build-up of oxidatively modified protein that results, at least in part, from impaired redox homeostasis associated with the aging process. Protein degradation and repair are critical for eliminating oxidized proteins from the cell. Oxidized protein degradation is mainly achieved by the proteasomal system and it is now well established that proteasomal function is generally impaired with age. Specific enzymatic systems have been identified which catalyze the regeneration of cysteine and methionine following oxidation within proteins. Protein-bound methionine sulfoxide diastereoisomers S and R are repaired by the combined action of the enzymes MsrA and MsrB that are subsequently regenerated by thioredoxin/thioredoxin reductase. Importantly, the peptide methionine sulfoxide reductase system has been implicated in increased longevity and resistance to oxidative stress in different cell types and model organisms. In a previous study, we reported that peptide methionine sulfoxide reductase activity as well as gene and protein expression of MsrA are decreased in various organs as a function of age. More recently, we have shown that gene expression of both MsrA and MsrB2 (Cbs-1) is decreased during replicative senescence of WI-38 fibroblasts, and this decline is associated with an alteration in catalytic activity and the accumulation of oxidized protein. In this review, we will address the importance of protein maintenance in the aging process as well as in replicative senescence, with a special focus on regulation of the peptide methionine sulfoxide reductase systems.

Aging↗
PubMed2004

The peptide methionine sulfoxide reductases, MsrA and MsrB (hCBS-1), are downregulated during replicative senescence of human WI-38 fibroblasts.

In contrast to other oxidative modifications of amino acids, methionine sulfoxide can be enzymatically reduced back to methionine in proteins by the peptide methionine sulfoxide reductase system, composed of MsrA and MsrB. The expression of MsrA and one member of the MsrB family, hCBS-1, was analyzed during replicative senescence of WI-38 human fibroblasts. Gene expression decreased for both enzymes in senescent cells compared to young cells, and this decline was associated with an alteration in catalytic activity and the accumulation of oxidized proteins during senescence. These results suggest that downregulation of MsrA and hCBS-1 can alter the ability of senescent cells to cope with oxidative stress, hence contributing to the age-related accumulation of oxidative damage.

Cell Line↗
PubMed2004

Enzymatic reactions involved in the repair of oxidized proteins.

Proteins are the targets of reactive oxygen species, and cell aging is characterized by a build-up of oxidized proteins. Oxidized proteins tend to accumulate with age, due to either an increase in the rate of protein oxidation, a decrease in the rate of oxidized protein repair and degradation, or a combination of both mechanisms. Oxidized protein degradation is mainly carried out by the proteasomal system, which is the main intracellular proteolytic pathway involved in protein turnover and the elimination of damaged proteins. However, part of the oxidative damage to cysteine and methionine residues, two amino acids which are highly susceptible to oxidation, can be repaired by various enzymatic systems that catalyze the reduction of cysteine disulfide bridge, cysteine-sulfenic and -sulfinic acids as well as methionine sulfoxide. The aim of this review is to describe these enzymatic oxidized protein repair systems and their potential involvement in the decline of protein maintenance associated with aging, focusing in particular on the methionine sulfoxide reductases system.

Animals↗
PubMed2002

Impairment of proteasome structure and function in aging.

Damage to macromolecules, and in particular protein, implicated in the cellular degeneration that occurs during the aging process, is corroborated by the accumulation of oxidative end-products over time. Oxidized protein build up is commonly seen as a hallmark of cellular aging. Protein turnover is essential to preserve cell function and the main proteolytic system in charge of cytosolic protein degradation is the proteasome. The proteasome is a multi-catalytic proteolytic complex, which recognizes and selectively degrades oxidatively damaged and ubiquitinated proteins. One of the hypothesis put forward to explain the accumulation of altered proteins is the decrease of proteasome activity with age. Indeed, accumulation of altered protein can be explained by increased protein alteration, decreased protein degradation or the combination of both. A short description of proteasome structure and of its role in cellular functions is first given. Then, accumulation of damaged protein is presented with emphasis on the pathways implicated in the formation of altered proteins. Finally, evidence for an age-related impairment of proteasome structure and function that has been reported by different groups is provided in the light of proteasomal dysfunction induced upon oxidative stress. It is now clear that proteasome activity is declining with age and that the loss in proteasome activity during aging is dependent of at least three different mechanisms: decreased proteasome expression; alterations and/or replacement of proteasome subunits and formation of inhibitory cross-linked proteins. However, it is also clear that events leading to the age- and disease-related loss of proteasome function have not yet been fully characterized.

Aging↗