Roles of heat shock factor 1 and 2 in response to proteasome inhibition: consequence on p53 stability.

International audienceA single heat shock factor (HSF), mediating the heat shock response, exists from yeast to Drosophila, whereas several related HSFs have been found in mammals. This raises the question of the specific or redundant functions of the different members of the HSF family and in particular of HSF1 and HSF2, which are both ubiquitously expressed. Using immortalized mouse embryonic fibroblasts (iMEFs) derived from wild-type, Hsf1(-/-), Hsf2(-/-) or double-mutant mice, we observed the distinctive behaviors of these mutants with respect to proteasome inhibition. This proteotoxic stress reduces to the same extent the viability of Hsf1(-/-)- and Hsf2(-/-)-deficient cells, but through different underlying mechanisms. Contrary to Hsf2(-/-) cells, Hsf1(-/-) cells are unable to induce pro-survival heat shock protein expression. Conversely, proteasome activity is lower in Hsf2(-/-) cells and the expression of some proteasome subunits, such as Psmb5 and gankyrin, is decreased. As gankyrin is an oncoprotein involved in p53 degradation, we analyzed the status of p53 in HSF-deficient iMEFs and observed that it was strongly stabilized in Hsf2(-/-) cells. This study points a new role for HSF2 in the regulation of protein degradation and suggests that pan-HSF inhibitors could be valuable tools to reduce chemoresistance to proteasome inhibition observed in cancer therapy

Ondes millimétriques et cellules nerveuses

National audienceD’ici 2020, des systèmes sans fil dans la bande de fréquences des 60 GHz, c’est-à-dire dans la gamme des ondes millimétriques (OMM), devrait gagner les foyers et les milieux professionnels. Cependant, on ne peut pas écarter la possibilité que ces nouveaux rayonnements puissent avoir des effets biologiques car les OMM sont utilisées en thérapie. Les OMM correspondent aux fréquences comprises entre 30 GHz et 300 GHz. Comparées aux radiofréquences utilisées en téléphonie mobile, les OMM sont absorbées par les tissus sur une très faible profondeur, donc essentiellement au niveau de la peau. L’objectif principal du projet "OMcell" est d’étudier l’impact potentiel des OMM sur des cultures de cellules présentant un phénotype neuronal

Études in vitro des effets biologiques des ondes millimétriques : expérimentation, instrumentation et dosimétrie

présentation oral

Études in vitro des effets biologiques des ondes millimétriques : expérimentation, instrumentation et dosimétrie

présentation oral

Ondes millimétriques - le point sur les effets biologiques à 40-60 GHz

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Millimeter-Wave Pulsed Heating in Vitro: Effect of Pulse Duration

International audienceThe aim of this work is to compare the response of A375 melanoma cells following 90 min of exposure to trains of 1.5 or 6 s millimeter-waves (MMW)-induced thermal pulses with the same temperature dynamics. Phosphorylation of heat shock protein 27 (HSP27) and activation of cleaved Caspase-3 were used as markers of cellular stress and apoptosis, respectively. Immunofluorescence was used to observe and precisely quantify the cellular response as a function of the spatial distribution within the exposed area. Results show that cellular response was stronger when cells were exposed to a train of 1.5 s compared to 6 s heat pulses despite the same average temperature dynamics. Cellular apoptosis induced by 1.5 s pulses was about 50% greater compared to the one induced by 6 s pulses in the area of maximal thermal stress. Similarly, HSP27 phosphorylation was approximately 20% stronger than the one induced by 6 s pulses, and mainly focused within a small area of a few mm(2). Cellular response to MMW induced by pulsed heating does not only depend on the peak, average, and minimum temperature. It is a function of combination of the pulse parameters, including duration, peak power, and period. MMW-induced heat pulses can be efficiently used to induce cellular stress and apoptosis in melanoma cells as a promising innovative tool for the treatment of superficial skin cancer. Adaptative therapies might be envisaged by tuning the pulse shape as a function of the desired effect

Interactions des ondes millimétriques avec le vivant

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