Aging and the Role of Reactive Nitrogen Species

Abstract

The role of reactive oxygen species and its effects on aging has received considerable attention in the past 47 years since Dr. Denham Harman first proposed the "free radical theory of aging." Though not completely understood due to the incalculable number of pathways involved, the number of manuscripts that facilitate the understanding of the underlying effects of reactive radical species on the oxidative stress on lipids, proteins, and DNA and its contribution to the aging process increases nearly exponentially each year. More recently, the role of reactive nitrogen species, such as nitric oxide and its by-products--nitrate (NO3-), nitrite (NO2-), peroxynitrite (ONOO-), and 3-nitrotyrosine--have been shown to have a direct role in cellular signaling, vasodilation, and immune response. Nitric oxide is produced within cells by the actions of a group of enzymes called nitric oxide synthases. Presently, there are three distinct isoforms of nitric oxide synthase: neuronal (nNOS or NOS-1), inducible (iNOS or NOS-2), and endothelial (eNOS or NOS-3), and several subtypes. While nitric oxide (NO*) is a relative unreactive radical, it is able to form other reactive intermediates, which could have an effect on protein function and on the function of the entire organism. These reactive intermediates can trigger nitrosative damage on biomolecules, which in turn may lead to age-related diseases due to structural alteration of proteins, inhibition of enzymatic activity, and interferences of the regulatory function. This paper will critically review the evidence of nitration and the important role it plays with aging. Furthermore, it will summarize the physiological role of nitration as well as the mechanisms leading to proteolytic degradation of nitrated proteins within biological tissues.

Antioxidative Effect of Rice Bran Oil and Medium Chain Fatty Acid Rich Rice Bran Oil in Arsenite Induced Oxidative Stress in Rats

“…Reactive oxygen species ROS can cause cell and tissue damage and lipid peroxidation, leading to impaired cellular function and alterations in the physico-chemical properties of cell membranes, which in turn disrupt vital functions 14 .…”

A Method for Selective Enrichment and Analysis of Nitrotyrosine-Containing Peptides in Complex Proteome Samples

“…[1][2][3][4][5] Increased levels of nitrotyrosine in a variety of tissues have been identified in over 80 different pathologies, 6 including various neurodegenerative diseases [6][7][8][9] as well as in normal biological aging. [10][11][12][13][14][15] Tyrosine nitration can alter protein structure and function, affect its biological half-life, inactivate enzymes and receptors that depend on tyrosine residues for their activity, and prevent phosphorylation of tyrosine residues important for signal transduction. 15,16 In addition, recent work has shown that tyrosine nitration can have a regulatory role in redox signaling.…”

Cutting Edge: MHC Class II-Restricted Peptides Containing the Inflammation-Associated Marker 3-Nitrotyrosine Evade Central Tolerance and Elicit a Robust Cell-Mediated Immune Response

“…3 Accumulation of protein-associated nitrotyrosine has been documented in inflammatory conditions of diverse origin such as atherosclerosis (1), respiratory disease (2), transplant rejection (3), multiple sclerosis (4), Alzheimer's disease (5), celiac disease (6), arthritis (7)(8)(9), ischemia-reperfusion injury (10), autoimmune diabetes (11), autoimmune uveitis (12), and infectious diseases (13). Although the precise molecular mechanism(s) responsible for in vivo formation of nitrotyrosine is still not firmly established, peroxynitrite and other reactive nitrogen species generated during periods of inflammation are thought to be primary intermediates (14,15).…”