1 / 24

J. Duranteau H ôpital de Bicêtre - Université Paris-Sud XI

Réponse cellulaire à l’hypoxie. J. Duranteau H ôpital de Bicêtre - Université Paris-Sud XI. Réponse cellulaire à l’ hypoxie. Hypoxie. Métabolisme oxydatif. Mitochondrie. Espèces radicalaires de l’oxygène. Dysfonction d’organe. Dysfonction endothéliale. Hepatocytes. Cardiomyocytes.

taurus
Download Presentation

J. Duranteau H ôpital de Bicêtre - Université Paris-Sud XI

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Réponse cellulaire à l’hypoxie J. Duranteau Hôpital de Bicêtre - Université Paris-Sud XI

  2. Réponse cellulaire à l’ hypoxie Hypoxie Métabolisme oxydatif Mitochondrie Espèces radicalaires de l’oxygène Dysfonction d’organe Dysfonction endothéliale

  3. Hepatocytes Cardiomyocytes Duranteau et al. J. Biol. Chem. 273:11619-11624. 1998.

  4. 1200 Normoxia 15% 02 Hypoxia 5% 02 1000 Hypoxia 3% 02 Hypoxia 1% 02 800 DCFH (% of initial values) Duranteau et al. J. Biol. Chem. 273:11619-11624. 1998. 600 400 200 0 Hypoxia -200 0 60 120 180 240 110 100 90 80 70 60 Total motion (% of initial values) 50 40 30 20 Hypoxia 10 0 0 60 120 180 240 Times (min)

  5. Duranteau et al. J. Biol. Chem. 273:11619-11624. 1998.

  6. ATP ADP + Pi

  7. adenine nucleotide translocase Flux d’électrons ATP ADP + Pi Fuite protons NADH / FADH2 ADP

  8. O2.- ATP ADP + Pi

  9. Hep3B Human Hepatoma Cells Guzy RD et al. CellMetabolism 2005

  10. Prolyl hydroxylases Wheaton W and Chandel ND Am J Physiol Cell Physiol, 2010.

  11. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia Lactate deshydrogènase A Pyruvate Deshydrogènase kinase 1 Pyruvate Deshydrogènase (PDH) Kim JW et al. Cell metabolism 2006

  12. Wheaton W and Chandel ND Am J Physiol Cell Physiol, 2010.

  13. Chen Z et al. Oncogene (2010) 29, 4362–4368

  14. Comellas AP et al. Circ Res. 2006;98:1314-1322.

  15.  ATP demand Gusarova AP et al. Molecular and Cellular Biology. 2009.

  16. Réponse cellulaire à l’ hypoxie Hypoxie Diminution du métabolisme oxydatif Retarde la dysoxie cellulaire Diminue la production d’ERO Dysfonction d’organe

  17. HIF prolyl hydroxylase 1-deficient (Egln2-/-) mice Aragones A et al. Nature Genetics 40, 170 - 180 (2008)

  18. Simerabet M et al.Brain research 2008

  19. Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction 58 patients with acute ST-elevation myocardial infarction intravenous bolus of 2.5 mg/kg of cyclosporine Piot C et al. NEJM 359;5 2008

  20. Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction 58 patients with acute ST-elevation myocardial infarction intravenous bolus of 2.5 mg/kg of cyclosporine Piot C et al. NEJM 359;5 2008

  21. Réponse cellulaire à l’ hypoxie Hypoxie Inflammation infection Métabolisme oxydatif Mitochondrie Espèces radicalaires de l’oxygène Dysfonction d’organe Dysfonction endothéliale

  22. Tumor Necrosis Factor Inhibits Oxidative Phosphorylation through Tyrosine Phosphorylation at Subunit I of Cytochrome c Oxidase Bovine and murine hepatocyte homogenates CcO activity 60% reduction in CcO activity Samavati L. et al. J. Biol. Chem. 283, pp. 21134–21144, 2008 Cytochrome C (μM)

  23. Tumor Necrosis Factor Inhibits Oxidative Phosphorylation through Tyrosine Phosphorylation at Subunit I of Cytochrome c Oxidase ATP (%) T 100 T Samavati L. et al. J. Biol. Chem. 283, pp. 21134–21144, 2008 80 T 60 40 T 20 0 - + - + TNFα H2.35 cells Liver tissue

  24. Réponse cellulaire à l’ hypoxie Hypoxie Métabolisme oxydatif Mitochondrie Espèces radicalaires de l’oxygène Dysfonction d’organe Dysfonction endothéliale

More Related