Les protéines de choc thermique (heat shock proteins). I : Classification, structure, fonctions et implications dans les processus pathologiques

All living systems have evolved mechanisms to maintain homeostasis in the face of rapid environmental changes. When exposed to elevated temperatures, most of the cells activate the synthesis of a specific group of proteins called Heat Shock Proteins (Hsps). This heat shock response, under control of specific transcription factors, the Heat Shock factors (HSF), is an evolutionarily conserved mechanism, from bacteria to humans. Heat Shock Proteins are classified into families according to their molecular weight (Hsp 25, 40, 70, 90, 105). They play the role of molecular chaperones by binding and protecting other molecules (proteins, RNAs). The function of Hsp is to prevent accumulation of non-native proteins either by assisting proper folding of polypeptides or by driving them to proteosome pathway for degradation. Hsps are involved in various pathological processes that are accompanied by protein alterations such as chronic or degenerative diseases. This review describes structural and functional characteristics of the six main Hsps classes. It also focuses on their respective role in highly studied pathologies. The diversity of Hsps implications in these diseases explains that they became recently a strategic target in development of new therapeutic strategies.Tout organisme est doté de mécanismes lui permettant de résister à de brusques changements de son environnement. Exposées à une température anormalement élevée, la plupart des cellules activent l’expression d’une classe particulière de protéines appelées les protéines de choc thermique (Heat Shock Proteins, Hsps). Cette réponse cellulaire au choc thermique placée sous le contrôle de facteurs de trans-cription spécifiques, les facteurs de choc thermique (Heat shock factor, HSF) est un mécanisme conservé au travers de l’évolution depuis les bactéries jusqu’à l’homme. Les protéines de choc thermique qui sont divisées en familles désignées par leur masse moléculaire (Hsp25, 40, 70, 90, 105) font partie des molé-cules chaperons qui s’associent à d’autres molécules (protéines, ARNs) et en protègent la destinée. Le rôle des Hsp est d’empêcher l’accumulation de protéines anormales en aidant à conformer correctement les polypeptides ou en les dirigeant vers le protéosome qui les détruit. En tant que chaperons, les Hsp sont impliquées dans de nombreux processus pathologiques qui s’accompagnent d’altérations des protéines comme les maladies chroniques et dégénératives. Cette revue décrit les spécificités structurelles et fonc-tionnelles des six familles principales d'Hsp ainsi que leur intervention à différents niveaux dans les patho-logies les mieux étudiées. La multiplicité de l'implication des Hsp dans ces phénomènes pathologiques les désigne comme cibles privilégiées dans le développement de nouvelles stratégies thérapeutiques

Cytotoxicity of Stimulated Equine Neutrophils on Equine Endothelial Cells in Culture

We studied the interactions of isolated equine neutrophils with endothelial cells in culture, mimicking a situation of acute inflammation. Our main purpose was to demonstrate that the supernatant of activated neutrophils was sufficient to damage endothelial cells. Equine endothelial cells (from carotid arteries) were covered either with increased numbers of equine neutrophils stimulated by phorbol myristate acetate, or with the supernatant collected after an in vitro stimulation of the neutrophils. Cytotoxicity was estimated by the release of preincorporated 51Cr, and by light microscopy observations. To assert the specific role of reactive oxygen species, endothelial cells were treated by the hypoxanthine/xanthine oxidase (X/XOx) system (production of superoxide anion and hydrogen peroxide), and by hypochlorite (product of the activity of myeloperoxidase). A strong cytotoxicity was found with stimulated neutrophils; microscopic observations indicated a loss of 50% of the endothelial cells and morphological alterations in the remaining cells. The supernatant of stimulated neutrophils was cytotoxic, in correlation with the number of neutrophils used to obtain the supernatant, and with the supernatant concentration of myeloperoxidase. The cytotoxicity of the X/XOx system was weak, but was increased by myeloperoxidase. Hypochlorite was highly toxic. We concluded that the supernatant of stimulated neutrophils was sufficient to obtain cytotoxic effects on the endothelium, in the absence of a direct contact between endothelium and neutrophils, and that this cytotoxicity was mainly linked to the activity of myeloperoxidase. From these in vitro results, it can be extrapolated that in pathologies characterised by an important activation of neutrophils, damage can spread to cells and tissues away from the inflammation focus

Immunocytochemical study of cell type distribution in the pituitary of barbus barbus (Teleostei, Cyprinidae)

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