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Stress oxydant et glycation : relation structure et activités biologiques de l'albumine in vitro et in vivo dans le cadre de la pathologie diabétique

Abstract : Numerous pathologies are strongly linked to structural and functional alteration of target proteins. Aggregation, glycation and oxidative damages constitute modifications of proteins, frequently observed in numerous states of disease. The biological activities of proteins and their conformational modifications are strictly connected. Among proteins, albumin represents the most abundant and the most important antioxidant in blood. This circulating protein can, in particular, undergo increased glycoxidation in case of diabetes, which can lead to the formation of Advanced Glycation Endproducts (AGEs), and so induce various deleterious effects on cells. In this study, I focused on the impact of aggregation, glycation and oxidative modifications on the structural, redox and antioxidant status of albumin and the effect of this altered protein on various cell lines physiology. I firstly investigated, using biochemical and biophysical techniques, the structural changes of bovine serum albumin induced by glycation, aggregation and both processes simultaneously. By this, I tried to elucidate the impact of these processes on the antioxidant properties of the modified protein. Secondly, I studied the oxidative activity of in vitro glycoxidized bovine serum albumin on mature adipocyte by identifying, in particular, specifically adipocyte carbonylated protein targets by using proteomic techniques. Then, I compared the effect of in vitro glucose and methylglyoxal-induced oxidative modifications on bovine serum albumin (BSA) and human serum albumin (HSA) protein structures and on THP1 monocyte physiology. At last, the best way to characterize the structural and functional modification of altered albumin is to study this protein with suitable pathological condition, in vivo instead of using an in vitro model. In this last part, I determined simultaneously the structure, the antioxidant properties and redox status of human plasma and its corresponding albumin purified from a panel of plasma, in order to confirm or invalidate predictions based on in vitro models. These investigations confirm the importance of native structure on functional properties of the most abundant and protective protein in the circulatory system and by the way to have a better understanding of its involvement in several physiological disorders such as Diabetes.
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Submitted on : Tuesday, October 19, 2010 - 10:55:50 AM
Last modification on : Monday, April 6, 2020 - 2:44:47 PM
Long-term archiving on: : Friday, October 26, 2012 - 11:40:36 AM

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  • HAL Id : tel-00527411, version 1

Citation

Philippe Rondeau. Stress oxydant et glycation : relation structure et activités biologiques de l'albumine in vitro et in vivo dans le cadre de la pathologie diabétique. Biochimie [q-bio.BM]. Université de la Réunion, 2009. Français. ⟨NNT : 2009lare0014⟩. ⟨tel-00527411⟩

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