TAILIEUCHUNG - Báo cáo khoa học: Pyruvate reduces DNA damage during hypoxia and after reoxygenation in hepatocellular carcinoma cells

Pyruvate is located at a crucial crossroad of cellular metabolism between the aerobic and anaerobic pathways. Modulation of the fate of pyruvate, in one direction or another, can be important for adaptative response to hypoxia followed by reoxygenation. | ễFEBS Journal Pyruvate reduces DNA damage during hypoxia and after reoxygenation in hepatocellular carcinoma cells Emilie Roudier Christine Bachelet and Anne Perrin Unite de Biophysique Cellulaire et Moleculaire IFR RMN biomedicale de la cellule a 1 homme CRSSA BP 87 La Tronche France Keywords DNA damage glutathione hypoxia pyruvate reoxygenation Correspondence A. Perrin CRSSA RBP Unite de biophysique cellulaire et moleculaire 24 Avenue des Maquis du Gresivaudan BP 87 38702 La Tronche Cedex France Fax Tel 33 4 76 63 68 79 E-mail aperrin@ Present address Departement de kinesiologie Universite de Montreal Canada Received 5 July 2007 revised 10 August 2007 accepted 14 August 2007 doi Pyruvate is located at a crucial crossroad of cellular metabolism between the aerobic and anaerobic pathways. Modulation of the fate of pyruvate in one direction or another can be important for adaptative response to hypoxia followed by reoxygenation. This could alter functioning of the antioxidant system and have protective effects against DNA damage induced by such stress. Transient hypoxia and alterations of pyruvate metabolism are observed in tumors. This could be advantageous for cancer cells in such stressful conditions. However the effect of pyruvate in tumor cells is poorly documented during hypoxia reoxygenation. In this study we showed that cells had a greater need for pyruvate during hypoxia. Pyruvate decreased the number of DNA breaks and might favor DNA repair. We demonstrated that pyruvate was a precursor for the biosynthesis of glutathione through oxidative metabolism in HepG2 cells. Therefore glutathione decreased during hypoxia but was restored after reoxygenation. Pyruvate had beneficial effects on glutathione depletion and DNA breaks induced after reoxygenation. Our results provide more evidence that the a-keto acid promotes the adaptive response to hypoxia followed by reoxygenation. Pyruvate might thus help to protect cancer .

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