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Anne-Laure Bulteau

Publications and source records attributed to Anne-Laure Bulteau.

14 recordsLinked to original sources
PubMed2006

Mitochondrial protein oxidation and degradation in response to oxidative stress and aging.

Mitochondria are a major source of intracellular reactive oxygen species (ROS), the production of which increases with age. These organelles are also targets of oxidative damage. The deleterious effects of ROS may be responsible for impairment of mitochondrial function observed during various pathophysiological states associated with oxidative stress and aging. An important factor for protein maintenance in the presence of oxidative stress is enzymatic reversal of oxidative modifications and/or protein degradation. Failure of these protein maintenance systems is likely a critical component of the aging process. Mitochondrial matrix proteins are sensitive to oxidative inactivation and oxidized proteins are known to accumulate during aging. The ATP-stimulated mitochondrial Lon protease is a highly conserved protease found in prokaryotes and the mitochondrial compartment of eukaryotes and is believed to play an important role in the degradation of oxidized mitochondrial matrix proteins. Age-dependent declines in the activity and regulation of this proteolytic system may underlie accumulation of oxidatively modified and dysfunctional protein and loss in mitochondrial viability.

Aging↗
PubMed2005

Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion.

Prooxidents can induce reversible inhibition or irreversible inactivation and degradation of the mitochondrial enzyme aconitase. Cardiac ischemia/reperfusion is associated with an increase in mitochondrial free radical production. In the current study, the effects of reperfusion-induced production of prooxidants on mitochondrial aconitase and proteolytic activity were determined to assess whether alterations represented a regulated response to changes in redox status or oxidative damage. Evidence is provided that ATP-dependent proteolytic activity increased during early reperfusion followed by a time-dependent reduction in activity to control levels. These alterations in proteolytic activity paralleled an increase and subsequent decrease in the level of oxidatively modified protein. In vitro data supports a role for prooxidants in the activation of ATP-dependent proteolytic activity. Despite inhibition during early periods of reperfusion, aconitase was not degraded under the conditions of these experiments. Aconitase activity exhibited a decline in activity followed by reactivation during cardiac reperfusion. Loss and regain in activity involved reversible sulfhydryl modification. Aconitase was found to associate with the iron binding protein frataxin exclusively during reperfusion. In vitro, frataxin has been shown to protect aconitase from [4Fe-4S](2+) cluster disassembly, irreversible inactivation, and, potentially, degradation. Thus, the response of mitochondrial aconitase and ATP-dependent proteolytic activity to reperfusion-induced prooxidant production appears to be a regulated event that would be expected to reduce irreparable damage to the mitochondria.

Aconitate Hydratase↗
PubMed2004

Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity.

Numerous degenerative disorders are associated with elevated levels of prooxidants and declines in mitochondrial aconitase activity. Deficiency in the mitochondrial iron-binding protein frataxin results in diminished activity of various mitochondrial iron-sulfur proteins including aconitase. We found that aconitase can undergo reversible citrate-dependent modulation in activity in response to pro-oxidants. Frataxin interacted with aconitase in a citrate-dependent fashion, reduced the level of oxidant-induced inactivation, and converted inactive [3Fe-4S]1+ enzyme to the active [4Fe-4S]2+ form of the protein. Thus, frataxin is an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation.

Aconitate Hydratase↗
PubMed2004

Are expanded polyglutamine proteins a proteasome substrate?

Protein degradation is essential to preserve cellular homeostasis since it is an important step in a variety of cellular processes. Among the intracellular proteolytic systems, the proteasome is considered to play a major role in basal protein turnover, that is, degradation of abnormal/damaged proteins. The accumulation of protein aggregates as well as various components of the ubiquitin/proteasome system raises the possibility that an impaired proteasome function may be a causal factor in the cellular degeneration that occurs in neurodegenerative disorders caused by expanded polyglutamine repeats.

Animals↗
PubMed2004

Algae extract protection effect on oxidized protein level in human stratum corneum.

Modification of proteins by reactive oxygen species is implicated in different disorders. The proteasome is a multicatalytic proteinase in charge of intracellular protein turnover and of oxidized proteins degradation. Consequently, proteasome function is very important in controlling the level of altered proteins in eukaryotic cells. Evidence for a decline in proteasome activity during skin photo-aging has been provided in Bulteau et al. in 2002. The ability of a lipid algae extract (Phaeodactylum tricornutum) to stimulate 20S proteasome peptidase activities was described by Nizard et al. in 2001. Furthermore, keratinocytes treated with Phaeodactylum tricornutum extract and then UVA and UVB irradiated, exhibited a sustained level of proteasome activity comparable to the one of nonirradiated cells. The level of modified proteins can be quantified by measurement of protein carbonyl content (Oxyblot technique), which has been shown to increase with aging and other disorders. In this paper, it is described that, in the presence of this lipid algae extract, the level of oxidized proteins is reduced, as assessed by the Oxyblot technique. These results are obtained both with culture of human keratinocytes and stratum corneum skin cells (obtained by stripping) from human volunteers. Altogether, these results argue for the presence of compounds in this algae extract that have a stimulating and/or protective effect on proteasome activity, resulting in a decreased level of protein oxidation.

Adult↗
PubMed2003

Redox-dependent modulation of aconitase activity in intact mitochondria.

It has previously been reported that exposure of purified mitochondrial or cytoplasmic aconitase to superoxide (O(2)(-)(*) or hydrogen peroxide (H(2)O(2)) leads to release of the Fe-alpha from the enzyme's [4Fe-4S](2+) cluster and to inactivation. Nevertheless, little is known regarding the response of aconitase to pro-oxidants within intact mitochondria. In the present study, we provide evidence that aconitase is rapidly inactivated and subsequently reactivated when isolated cardiac mitochondria are treated with H(2)O(2). Reactivation of the enzyme is dependent on the presence of the enzyme's substrate, citrate. EPR spectroscopic analysis indicates that enzyme inactivation precedes release of the labile Fe-alpha from the enzyme's [4Fe-4S](2+) cluster. In addition, as judged by isoelectric focusing gel electrophoresis, the relative level of Fe-alpha release and cluster disassembly does not reflect the magnitude of enzyme inactivation. These observations suggest that some form of posttranslational modification of aconitase other than release of iron is responsible for enzyme inactivation. In support of this conclusion, H(2)O(2) does not exert its inhibitory effects by acting directly on the enzyme, rather inactivation appears to result from interaction(s) between aconitase and a mitochondrial membrane component responsive to H(2)O(2). Nevertheless, prolonged exposure of mitochondria to steady-state levels of H(2)O(2) or O(2)(-)(*) results in disassembly of the [4Fe-4S](2+) cluster, carbonylation, and protein degradation. Thus, depending on the pro-oxidant species, the level and duration of the oxidative stress, and the metabolic state of the mitochondria, aconitase may undergo reversible modulation in activity or progress to [4Fe-4S](2+) cluster disassembly and proteolytic degradation.

Aconitate Hydratase↗
PubMed2002

Impairment of proteasome function upon UVA- and UVB-irradiation of human keratinocytes.

The major environmental influence for epidermal cells is sun exposure and the harmful effect of UV radiation on skin is related to the generation of reactive oxygen species that are altering cellular components including proteins. It is now well established that the proteasome is responsible for the degradation of oxidized proteins. Therefore, the effects of UV-irradiation on proteasome have been investigated in human keratinocyte cultures. Human keratinocytes were irradiated with 10 J/cm(2) of UVA and 0.05 J/cm(2) of UVB and proteasome peptidase activities were measured in cell lysates using fluorogenic peptides. All three peptidase activities were decreased as early as 1 h and up to 24 h after irradiation of the cells. Increased levels of oxidized and ubiquitinated proteins as well as proteins modified by the lipid peroxidation product 4-hydroxy-2-nonenal were also observed in irradiated cells. However, immunopurified 20S proteasome exhibited no difference in both peptidase specific activities and 2D gel pattern of subunits in irradiated cells, ruling out the possibility that the 20S proteasome could be a target for the UV-induced damage. Finally, extracts from irradiated keratinocytes were able to inhibit degradation by the proteasome, demonstrating the presence of endogeneous inhibitors, including 4-hydroxy-2-nonenal modified proteins, generated upon UV-irradiation.

Aldehydes↗
PubMed2002

Age-dependent declines in proteasome activity in the heart.

The proteasome is a major intracellular proteolytic system involved in the removal of oxidized and ubiquitinated protein and the induction of certain stress response pathways. In this study, age-dependent alterations in proteasome function were investigated to gain insight into potential factors which contribute to increased susceptibility to various forms of heart disease during aging. Proteasome activity in cellular extracts prepared from Fisher 344 rat hearts was found to decrease with age. These declines in activity were associated with a decreased 20S proteasome content and loss of specific activities. As determined by two-dimensional gel electrophoresis of purified 20S proteasome, the distribution and silver staining intensities of enzyme subunits were found to vary with age, suggesting that alterations in proteasome subunit composition and/or structure are involved in age-related declines in proteasome activity. In addition, age-dependent increases in the levels of oxidized and ubiquitinated proteins, known substrates of the proteasome, were observed. Thus, loss in proteasome function may impair the ability of myocytes to mount an appropriate response to stress, thereby enhancing the susceptibility of the aging heart to cardiovascular disease.

Aging↗
PubMed2002

Aortic vasoreactivity during prolonged hypoxia and hypoxia-reoxygenation in senescent rats.

To determine the effects of prolonged hypoxia and hypoxia-reoxygenation in senescent blood vessels, isolated aortic rings from 4- and 24-month-old (mo) Wistar rats were submitted to prolonged hypoxia (50 min) or hypoxia/reoxygenation (20 min/30 min) and contractile function recorded. Phenylephrine-induced contraction and sodium nitroprusside- and acetylcholine-induced relaxations were measured after hypoxia or after hypoxia/reoxygenation. In 24 mo group, prolonged hypoxia increased (+83%, P<0.01) and prolonged initial hypoxic contraction, while hypoxic relaxation and delayed contraction were unchanged. Relaxation to acetylcholine was more reduced than in 4 mo group while contraction to phenylephrine and relaxation to sodium nitroprusside were similarly impaired. During reoxygenation, contraction was of same amplitude at both ages and the relaxation to acetylcholine was impaired but to a similar extent in both groups. In conclusion, hypoxic stress induces a greater endothelium-injury in senescent aorta, and increased transient hypoxic contraction, without aggravation of late hypoxic contraction. Aging does not exacerbate the impairment of aortic vasoreactivity after hypoxia-reoxygenation, especially endothelium-dependent relaxation, in sharp contrast to prolonged hypoxia. These age-related changes in vascular sensitivity to oxygen deprivation are different from those observed in coronary arteries, indicating that vasoreactivity during such pathological stress strongly depends on the type of vessel, especially during aging.

Acetylcholine↗
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↗
PubMedDate not supplied

Algae extract-mediated stimulation and protection of proteasome activity within human keratinocytes exposed to UVA and UVB irradiation.

Sun exposure is the major environmental influence for epidermal cells; the harmful effect of UV radiation on skin is related to the generation of reactive oxygen species that alter cellular components including proteins. It is now well established that the proteasome is responsible for the degradation of most of oxidized proteins and that impairment of proteasome function is a hallmark of cellular aging. In a previous study, we investigated the effects of UV irradiation on proteasomes in human keratinocyte cultures and showed that all three peptidase activities were decreased 24 h after irradiation of the cells. Increased levels of oxidatively modified proteins were observed in irradiated cells and were found to act as endogenous inhibitors of the proteasome. We report here on the stimulating and protective effects of an algae extract, prepared from Phaeodactylum tricornutum, on proteasome peptidase activities of human keratinocytes exposed to UVA and UVB irradiation. In addition, preserving proteasome function resulted in lowering the extent of the irradiation-induced protein oxidative damage, opening up new strategies for protection of epidermal cells against the detrimental effects of UV irradiation.

Cell Culture Techniques↗
PubMedDate not supplied

UV and proteasomes.

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Cysteine Endopeptidases↗