pr a. avignon, mgsd, istambul 04/2007 the unified concept of oxidative stress pr a. avignon service...

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Pr A. Avignon, MGSD, Istambul 04/2 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

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Page 1: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

The Unified Concept ofOxidative Stress

Pr A. AvignonService des Maladies MétaboliquesHôpital LapeyronieMontpellier

Page 2: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

The Unified Concept ofOxidative Stress

The Unified Concept ofOxidative Stress

OxidativeStress

OxidativeStress

Page 3: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

What is Oxidative Stress ?

What is Oxidative Stress ?

ANTIOXIDANTSANTIOXIDANTSOXIDANTSOXIDANTS

Oxygen Free RadicalsOxygen Free RadicalsNitrogen Free RadicalsNitrogen Free Radicals

Specific EnzymesSpecific EnzymesVitamin E, Vitamin C,Vitamin E, Vitamin C,Carotenoids, SeleniumCarotenoids, Selenium

Page 4: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Free RadicalsFree Radicals

Any molecule containing one or more unpaired electrons

Reactive Oxygen Species (ROS) -

Reactive Nitrogen Species (RNS) - NO. Reactive Metabolites or Intermediates

- metabolic activation of drugs, toxins, pollutants, cigarette smokes, etc.

Page 5: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Reactive Oxygen Species (ROS)

Reactive Oxygen Species (ROS) Superoxide (O2

.-)

Hydrogen Peroxide (H2O2) Hydroxyl Radical (OH.) - product of

Fenton reaction catalyzed by free Fe and Cu

Singlet Oxygen (1gO2) - oxygen at an excited state, requiring photosensitizers and photons

Page 6: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Sources of oxygen free radicals

Sources of oxygen free radicals

Page 7: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Free Radical Defense System

Free Radical Defense System

Page 8: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Oxidative Stress: Consequences

Oxidative Stress: Consequences

Page 9: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Obesity-induced oxidative stress

Obesity-induced oxidative stress

Page 10: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Fatty Acids -Induced Oxidant Stress

Fatty Acids -Induced Oxidant Stress

J Clin Endocrinol Metab 81:4244-4248, 1996

Page 11: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Obesity-Induced Oxidant Stress and Insulin Resistance

Obesity-Induced Oxidant Stress and Insulin Resistance

Muscle Cells

Page 12: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

Green K et al, Diabetes 53 (Suppl. 1):S110, 2004

Role of ß-cell mitochondria in sensing increases in plasma glucose and inducing insulin secretion.

Page 13: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

Diabetes 53 (Suppl. 1):S119–S124, 2004

Page 14: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Sensibility to oxidative stress Oxidative stress increased by

FFA FFA acids and oxidative stress

induce apoptosis of B-cells

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

ß-Cell Toxicity, and Oxidative Stress in Type 2 Diabetes

Diabetes 53 (Suppl. 1):S119–S124, 2004

Page 15: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Hyperglycemia / Oxidant Stress / Diabetic Complications

Hyperglycemia / Oxidant Stress / Diabetic Complications

Glucose-6-P

Hexokinase

Phosphohexoisomérase

Extra-cellular glucose

Fructose-6-P

Glyceraldéhyde-3-P

1,3-Diphosphoglycérate

GLUT-1

KidneyRetina

Neurones

pyruvate

Acetyl CoA

PDH

Cycle de

Krebs

Pyruvate

Page 16: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Glucose-6-P

Hexokinase

Phosphohexoisomérase

Glucose extra cellulaire

Fructose-6-P

Glyceraldéhyde-3-P

1,3-Diphosphoglycérate

Voie des Polyols

Voie des Hexosamines

Voie de la Protéine Kinase C (PKC)

Voie des Produits Terminaux de la Glycation

Hyperglycemia Oxidative Stress Diabetic Complications

Hyperglycemia Oxidative Stress Diabetic Complications

Page 17: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

International Journal of Obesity (2006) 30, 400–418.

Hyperglycemia / Oxidative Stress / Diabetic Complications

Hyperglycemia / Oxidative Stress / Diabetic Complications

Page 18: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007Nature 404, 787 - 790 (2000)

Hyperglycemia / Oxidative Stress / Diabetic Complications

Hyperglycemia / Oxidative Stress / Diabetic Complications

Page 19: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Conclusion

Conclusion

OxidativeStress

OxidativeStress

OxidativeStress

Page 20: Pr A. Avignon, MGSD, Istambul 04/2007 The Unified Concept of Oxidative Stress Pr A. Avignon Service des Maladies Métaboliques Hôpital Lapeyronie Montpellier

Pr A. Avignon, MGSD, Istambul 04/2007

Merci