Nitric Oxide and Peroxynitrite in Health and Disease

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http://intl-physrev.physiology.org/cgi/content/full/87/1/315

Nitric Oxide and Peroxynitrite in Health and Disease

Pál Pacher, ph S. Beckman and Lucas Liaudet

Section on Oxidative Stress Tissue Injury, Laboratory of Physiologic Studies, National Institutes of Health, National Institute of Alcohol Abuse and Alcoholism, Bethesda, land; Linus ing Institute, Department of Biochemistry and Biophysics, 2011 Agricultural and Life Sciences, Oregon State University, Corvallis, Oregon; and Department of Intensive Care Medicine, University Hospital, Lausanne, Switzerland

ABSTRACT

I. INTRODUCTION

II. NITRIC OXIDE

A. Discovery of Nitric Oxide as a Biological Molecule

B. The Selective Reactivity of Nitric Oxide

C. Diffusion and Signaling Properties of Nitric Oxide

D. Cytotoxic Effects of Nitric Oxide

E. Superoxide and the Hydroxyl Radical Theory of Radical Damage

III. PEROXYNITRITE

A. Historical Perspectives

B. Biological Chemistry

C. The Reverse Reaction of Peroxynitrite to Form Superoxide and Nitric Oxide

IV. PEROXYNITRITE-INDUCED CYTOTOXICITY

A. Mechanisms of Peroxynitrite-Mediated Oxidations

B. Biological Targets of Peroxynitrite

1. Proteins

A) REACTIONS OF PEROXYNITRITE WITH TRANSITION METAL CENTERS.

REACTIONS OF PEROXYNITRITE WITH AMINO ACIDS.

2. Lipids

3. Nucleic acids

C. Peroxynitrite, Mitochondria, and Cell Death

1. Peroxynitrite and apoptosis

2. Peroxynitrite and necrosis: the role of PARP

V. PEROXYNITRITE AND CELL SIGNALING

A. An Overview of Cell Signal Transduction

B. Modulation of Cell Signaling by Peroxynitrite

1. Inhibition of phosphotyrosine-dependent signaling

2. Activation of phosphotyrosine-dependent signaling

3. Peroxynitrite and MAPK signaling

A) ERK PATHWAY.

JNK PATHWAY.

C) P38 MAPK.

4. PI3K/protein kinase B (Akt) pathway

5. PKC pathway

6. NFkappaB

VI. NITRIC OXIDE AND PEROXYNITRITE IN DISEASE

A. Nitric Oxide and Peroxynitrite in Cardiac Diseases

1. Cardiovascular effects of peroxynitrite in vitro and in vivo, potential targets of peroxynitrite-induced toxicity in the cardiovascular system

2. Myocardial I/R injury

3. Preconditioning, postconditioning, and development of nitrate tolerance

4. Myocarditis, transplant coronary artery disease, and cardiac allograft rejection

5. Chronic heart failure

B. Nitric Oxide and Peroxynitrite in Vascular Diseases

1. Atherosclerosis and restenosis

2. Aging

3. Hypertension

C. Nitric Oxide and Peroxynitrite in Circulatory Shock

1. Mechanisms of tissue injury by peroxynitrite during circulatory shock

2. Role of peroxynitrite in the pathophysiological alterations of circulatory shock

A) PERIPHERAL VASCULAR FAILURE.

VASCULAR ENDOTHELIAL DYSFUNCTION.

C) MYOCARDIAL DEPRESSION.

D) SYSTEMIC INFLAMMATION.

E) TISSUE LEUKOCYTE SEQUESTRATION.

F) GUT MUCOSAL BARRIER FAILURE.

D. Nitric Oxide and Peroxynitrite in Local Inflammation

1. Chronic arthritis

2. Inflammatory bowel diseases

3. Tissue inflammation from toxic origin

E. Nitric Oxide and Peroxynitrite in Cancer

F. Nitric Oxide and Peroxynitrite in Stroke and Other Forms of Reperfusion Injury

1. Stroke

A) ROLE OF NO IN NORMAL BRAIN PHYSIOLOGY AND DURING ISCHEMIC STROKE.

ROLE OF PEROXYNITRITE IN NO-DEPENDENT NEUROTOXICITY IN STROKE.

2. Other forms of reperfusion injury

A) KIDNEY.

GUT.

C) LIVER.

D) LUNG.

G. Nitric Oxide and Peroxynitrite in Neurodegenerative Disorders

1. Multiple sclerosis (MS)

2. Parkinson's disease

3. Alzheimer's disease

4. Amyotrophic lateral sclerosis (ALS)

5. Huntington's disease

6. Traumatic brain injury

H. Nitric Oxide and Peroxynitrite in Diabetes and Diabetic Complications

1. Primary diabetes

2. Diabetic cardiovascular dysfunction

3. Diabetic neuropathy, nephropathy, and retinopathy

VII. CONCLUSIONS AND FUTURE PERSPECTIVES

GRANTS

ACKNOWLEDGMENTS

REFERENCES

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