Impact of leptin on ROS production in human mammary epithelial cells is dependent of neoplasic

Autor: Mahbouli, Sinda, Ortega , Sophie, Rouge, Stéphanie, VASSON, Marie-Paule, Rossary, Adrien
Přispěvatelé: Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Nutrition Humaine, CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Cancéropôle Lyon Auvergne Rhône-Alpes, Centre de Recherche en Nutrition Humaine (CRNH). FRA., Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Clermont-Ferrand, Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne, Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: ICTRNH 2013 Second International Congress of Translational Research in Human Nutrition Integrative Approaches in Nutrition Research
ICTRNH 2013 Second International Congress of Translational Research in Human Nutrition Integrative Approaches in Nutrition Research, Mar 2013, Clermont-Ferrand, France. 2013
2013; ICTRNH 2013 Second International Congress of Translational Research in Human Nutrition Integrative Approaches in Nutrition Research, Clermont-Ferrand, FRA, 2013-03-08-2013-03-09
Popis: Presenting author: Adrien Rossary The Second International Congress of Translational Research in Human Nutrition is organised by the Research Centre in Human Nutrition (CRNH) of Auvergne, of which INRA is a member, in collaboration with NuGO, European Association of universities and research institutes in the field of nutrigenomics; Nutritional status and hormonal factors, such as leptin, an adipokine highly regulated inobesity, induce cellular signaling pathways, some of which involving reactive oxygen species (ROS) asintracellular messenger. High levels of ROS contribute to oxidative stress, cellular damages andpathogenesis. That’s why ROS production associated to obesity could be a major risk factor ofmammary carcinogenesis.This study aimed to determine leptin effects on ROS production in 3 human epithelial mammary cellmodels which present different neoplasic status (healthy primary (HP) cells, MCF-7 and MDAMB-231). ROS production is measured by fluorescence in presence of two leptin concentrations (10ng/ml close to physiological values, 100 ng/ml as obesity level) with several probes at 2μM(Dichlorofluorescein (DCF) for total cellular ROS, Diaminofluorescein (DAF) for NO,Dihydrorhodamine (DHR) for mitochondrial ROS and Dihydroethidine (DHE) for cytosolic superoxydeanion (O2°-). Gene expression and catalytic activities of ROS production systems (NADPH oxidases,NO synthases, Dual oxidases) and of anti-oxidant enzymes (glutathione reductase, heme oxygenase,glutathione S-transferase) are performed.Whatever the cell model and the leptin concentration, a slight increase of total cellular ROSproduction is observed. This increase is independent of mitochondrial activity as DHR signalremained stable for HP cells (5.51 ± 0.40 RFU) and decreased for MCF7 and MDAMB-231 cells.Inversely, this ROS increase is dependent of cytosolic O2°- production as shown by DHE signalenhanced for HP cells (0.66 ± 0.01 to 0.81 ± 0.01 RFU), for MCF7 (0.79 ± 0.02 to 0.89 ± 0.03 RFU) andfor MDAMB-231 (0.82 ± 0.01 to 0.89 ± 0.02 RFU). Interestingly, this ROS production is dependent ofthe NADPH oxidase 5 (Nox5) expression and contributes to a different antioxidative response inregard to the neoplasic cell status. Leptin activates, only in HP cells, the antioxidative enzymesexpression and activities such as heme oxygenase or glutathione reductase.These data suggest that leptin could modulate the oxidative status of epithelial mammary cells indifferent ways according to the neoplasic cell status. Therefore leptin induces a similar ROSproduction for the 3 cell models whereas the anti oxidant cell response is not modified in MCF-7 andMA-MB-231 cells. This study highlights lower capacities of neoplasic cells to fight against oxidativestress.
Databáze: OpenAIRE
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