Superoxide Anion Radical (O·̄2), Superoxide Dismutases, and Related Matters

Fridovich, Irwin

doi:10.1074/jbc.272.30.18515

Cited by 1,152 publications

(745 citation statements)

References 73 publications

Supporting

Mentioning

695

Contrasting

Unclassified

Order By: Relevance

“…A major form of oxidative stress is initiated by transition metals in Fenton-type reactions that generate OH radicals (Fridovich, 1997). One key system to detoxify free metals is metallothioneins.…”

Section: Mitochondrial Protective and Repair Systemsmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

162

141

View full text Add to dashboard Cite

Oxidative stress occurs when the level of prooxidants exceeds the level of antioxidants in cells resulting in oxidation of cellular components and consequent loss of cellular function. Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al., 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production. Superoxide production precedes subsequent reactions that form potentially more dangerous reactive oxygen species (ROS) species such as the hydroxyl radical (˙OH), hydrogen peroxide (H 2 O 2 ) and peroxynitrite (OONO -). The major source of ROS in the mitochondria, and in the cell overall, is leakage of electrons from complexes I and III of the electron transport chain. It is estimated that 0.2-2% of oxygen taken up by cells is converted to ROS, through mitochondrial superoxide generation, by the mitochondria (Hansford et al., 1997). Generation of superoxide at complex I and III has been shown to occur at both the matrix side of the inner mitochondrial membrane and the cytosolic side of the membrane (Kakkar and Singh 2007). While exogenous sources of ROS such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins may contribute to the oxidative milieu, mitochondria are perhaps the most significant contribution to ROS production affecting the aging process. In addition to producing ROS, mitochondria are also a target for ROS which in turn reduces mitochondrial efficiency and leads to the generation of more ROS in a vicious self-destructive cycle. Consequently, the mitochondria have evolved a number of antioxidant and key repair systems to limit the damaging potential of free oxygen radicals and to repair damaged proteins (Figure 1.0). The aging eye appears to be at considerable risk from oxidative stress. This review will outline the potential role of mitochondrial function and redox balance in age-related eye diseases, and detail how the methionine sulfoxide reductase (Msr)

show abstract

Section: Mitochondrial Protective and Repair Systemsmentioning

confidence: 99%

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Brennan¹,

Kantorow²

2009

Experimental Eye Research

162

141

View full text Add to dashboard Cite

show abstract

“…ROS production in vessels, as well as other organs, including the heart, kidneys and brain, likely participate in blood pressure regulation. [30][31][32] This review will focus on ROS, the vascular system and hypertension, specifically relating to the clinical significance. All vascular cell types produce ROS, including endothelial, smooth muscle, adventitial fibroblasts and perivascular adipocytes, and can be formed by many enzymes, including xanthine oxidoreductase, uncoupled nitric oxide synthase, mitochondrial respiratory enzymes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [37][38][39][40][41][42][43][44] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Reactive oxygen species and vascular biology: implications in human hypertension

2010

View full text Add to dashboard Cite

Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension.

show abstract

“…Reactive oxygen species (ROS) are ubiquitous, highly reactive, diffusible molecules, including superoxide anions, hydrogen peroxide, hydroxyl radical, and nitric oxide (Fridovich, 1997). Cells generate ROS intracellularly and may release them extracellularly (Karlsson and Dahlgren, 2002;Kopprasch et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells

Yang

Elner

Bian

et al. 2007

Experimental Eye Research

361

251

View full text Add to dashboard Cite

Reactive oxygen species (ROS) generated during inflammation are believed to play critical roles in various ocular diseases. However, the underlying mechanisms remain poorly understood. We investigated if pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), and interferon-γ (IFN-γ), induce ROS in human retinal pigment epithelial (RPE) cells. TNF-α, IL-1β and IFN-γ increased both intracellular and extracellular ROS production in a time-and dosedependent manner. Thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial respiratory chain, blocked TNF-α-and IFN-γ-, but not IL-1β-induced ROS, whereas other two mitochondrial respiratory chain inhibitors, rotenone and antimycin A, had no effect. NADPH oxidase inhibitor (diphenylene iodinium) abolished the ROS production induced by IL-1β or IFN-γ, but not by TNF-α, whereas 6-aminonicotinamide (6AN), an inhibitor of the hexose monophosphate shunt (HMS), had no significant effects on the ROS induced by all three cytokines. ROS scavengers, pyrrolidinedithiocarbamate (PDTC) and N-acetyl-cysteine (NAC), reduced the levels of ROS induced by TNF-α, IL-1β and IFN-γ (P < 0.05). Collectively, these results demonstrate that TNF-α, IL-1β and IFN-γ increase mitochondrial-and NADPH oxidase-generated ROS in human RPE cells.

show abstract

Superoxide Anion Radical (O·̄2), Superoxide Dismutases, and Related Matters

Cited by 1,152 publications

References 73 publications

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

Reactive oxygen species and vascular biology: implications in human hypertension

Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells

Contact Info

Product

Resources

About