Osmoadaptation cellulaire cérébrale en situation d'hypertonicité systémique chez le rat (expession des gènes osmoprotecteurs et de leur facteur de transcription transactivateur)

Les observations cliniques suggèrent que les cellules du cerveau possèdent une capacité d'osmoadaptation. Dans un modèle animal d'hypertonicité systémique, nous avons étudié, au niveau du cerveau par immunocytochimie et hybridation in situ, l'expression cellulaire des gènes osmoprotecteurs aldose réductase (AR) et transporteur du myo-inositol (SMIT) et celle de leur facteur de transcription transactivateur (TonEBP). L'expression osmo-induite de TonEBP est restreinte aux neurones, celle de AR et de SMIT à certaines sous-populations respectivement neuronales et non-neuronales. Cette divergence d'expression cellulaire suggère l'implication d'autres gènes. Par biopuce, nous avons identifié quatre gènes précoces codant des facteurs de transcription et un transporteur des acides aminés neutres dont l'expression est osmo-induite dans le tissu cérébral et qui sont potentiellement impliqués dans l'osmoadaptation celluaire cérébraleClinical observations suggest that brain cells possess osmoadaptation ability. Using an animal model of systemic hypertonicity, we have studied by immunocytochemistry and in situ hybridization cellular expression of osmoprotective genes, aldose reductase (AR) and myo-inositol transporter (SMIT) and their transactivator transcription factor (TonEBP). TonEBP is expressed and tonicity-induced in neurons only. Tonicity-induced expression of AR and SMIT is restricted to respectively some neuronal and non-neuronal cell subsets. These large discrepancies in cellular expression suggest the involvement of other genes. Using microarray analysis, we have identified four immediate early genes encoding transcription factors and one neutral aminoacid transporter whose tissular expression is tonicity-induced in brain and which might be involved in brain cellular osmoadaptationLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Metabolomics Provides Novel Insights into the Potential Toxicity Associated with Heated Tobacco Products, Electronic Cigarettes, and Tobacco Cigarettes on Human Bronchial Epithelial BEAS-2B Cells

Smoking is an established risk factor for various pathologies including lung cancer. Electronic cigarettes (e-cigs) and heated tobacco products (HTPs) have appeared on the market in recent years, but their safety or, conversely, their toxicity has not yet been demonstrated. This study aimed to compare the metabolome of human lung epithelial cells exposed to emissions of e-cigs, HTPs, or 3R4F cigarettes in order to highlight potential early markers of toxicity. BEAS-2B cells were cultured at the air–liquid interface and exposed to short-term emissions from e-cigs set up at low or medium power, HTPs, or 3R4F cigarettes. Untargeted metabolomic analyses were performed using liquid chromatography coupled with mass spectrometry. Compared to unexposed cells, both 3R4F cigarette and HTP emissions affected the profiles of exogenous compounds, one of which is carcinogenic, as well as those of endogenous metabolites from various pathways including oxidative stress, energy metabolism, and lipid metabolism. However, these effects were observed at lower doses for cigarettes (2 and 4 puffs) than for HTPs (60 and 120 puffs). No difference was observed after e-cig exposure, regardless of the power conditions. These results suggest a lower acute toxicity of e-cig emissions compared to cigarettes and HTPs in BEAS-2B cells. The pathways deregulated by HTP emissions are also described to be altered in respiratory diseases, emphasizing that the toxicity of HTPs should not be underestimated