Potential Benefits of Peroxynitrite

Nossaman, Bobby D.; Kadowitz, Philip J.

doi:10.2174/1874143600802010031

Cited by 15 publications

(13 citation statements)

References 257 publications

(689 reference statements)

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“…In several reports concerning MIRPC, it has been demonstrated that iNOS and NO are involved in MIRPC-mediated protection in the heart (2, 44) and brain (4,48). Although many experiments have reported that peroxynitrite, a product of NO and superoxide, is a cytotoxic molecule, recent several studies have demonstrated that peroxynitrite plays a role as a vasodilator and inhibitor of platelet aggregation and inflammatory cell adhesion (26,30,31), all of which are beneficial to I/R injury. Thus the reduced renoprotection due to reduced iNOS expression may be associated with the reduced beneficial effect of peroxynitrite.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice

Kim

Jang

Park

2010

American Journal of Physiology-Renal Physiology

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Kim J, Jang HS, Park KM. Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice. Am J Physiol Renal Physiol 298: F158 -F166, 2010. First published October 28, 2009 doi:10.1152/ajprenal.00474.2009.-Ischemic preconditioning by a single event of ischemia and reperfusion (SIRPC) dramatically protects renal function against ischemia and reperfusion (I/R) induced several weeks later. We recently reported that reactive oxygen species (ROS) and oxidative stress were sustained in a kidney that had functionally recovered from I/R injury, thus suggesting an association between SIRPC and ROS and oxidative stress. However, the role of ROS in SIRPC remains to be clearly elucidated. To assess the involvement of ROS in SIRPC, mice were subjected to SIRPC (30 min of bilateral renal ischemia and 8 days of reperfusion) and then exposed to I/R injury. Thirty minutes of bilateral renal ischemia in the non-SIRPC mice resulted in a marked increase in plasma creatinine levels 4 and 24 h after reperfusion, which was not observed in the I/R in the SIRPC mice. SIRPC resulted in increases in the levels of kidney superoxide. Administrations of manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin [MnTMPyP; a cell-permeable superoxide dismutase (SOD) mimetic] and N-acetylcysteine (NAc; a ROS scavenger) to SIRPC mice blocked the SIRPC-induced increase in superoxide levels and removed ϳ48 -64% of the functional protection of the SIRPC kidney. Additionally, these administrations significantly inhibited I/R-induced increases in superoxide formation, hydrogen peroxide production, and lipid peroxidation, along with the inhibition of I/R-induced reductions in the expression and activity of manganese SOD, copper-zinc SOD, and catalase. Furthermore, administrations of MnTMPyP or NAc inhibited the SIRPC-induced increase in inducible nitric oxide synthase expression but did not inhibit the SIRPC-induced increases in heat shock protein-25 expression. In conclusion, the renoprotection afforded by SIRPC was triggered by ROS generated by SIRPC.acute kidney injury; renoprotection; inducible nitric oxygen synthase; heat shock protein ISCHEMIA AND REPERFUSION (I/R) causes acute kidney injury (AKI), which is characterized by high mortality and morbidity, and no effective therapeutic strategy has yet been developed for this condition (3). In addition to direct hypoxic damages induced by reductions in blood flow, I/R injury is associated with a number of factors, including reactive oxygen species (ROS), cytokines, and chemokines, all of which are abundantly generated during I/R (3, 39).ROS are generated under physiological and pathological conditions (9, 38). In physiological conditions, cells produce small amounts of ROS, which could be managed by the scavenging capacity of cells; whereas in pathological conditions they produces excessive ROS, beyond their capacity to scavenge it (9, 29, 38). This excessive ROS generation induces lipid peroxidation, inactivation o...

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Section: Discussionmentioning

confidence: 99%

Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice

Kim

Jang

Park

2010

American Journal of Physiology-Renal Physiology

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“…In fact, there have been some reports suggesting that NO donors, such as L-arginine, may protect the kidneys against I/R injury (2), whereas NO inhibitors may exacerbate kidney I/R injury (14). It was also recently reported that peroxynitrite, a product of nitric oxide and superoxide, is a known potent free radical metabolite that induces oxidative stress, functions as a vasodilator, and inhibits platelet aggregation and inflammatory cell adhesion, thus ameliorating or reducing I/R injury (16,(25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Endotoxin-induced renal tolerance against ischemia and reperfusion injury is removed by iNOS, but not eNOS, gene-deletion

Kim

Jang²,

Park

2010

BMB Reports

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Endotoxin including lipopolysaccharide (LPS) confers organ tolerance against subsequent challenge by ischemia and reperfusion (I/R) insult. The mechanisms underlying this powerful adaptive defense remain to be defined. Therefore, in this study we attempted to determine whether nitric oxide (NO) and its associated enzymes, inducible NOS (iNOS) and endothelial NOS (eNOS, a constitutive NOS), are associated with LPS-induced renal tolerance against I/R injury, using iNOS (iNOS knock-out) or eNOS (eNOS knock-out) gene-deleted mice. A systemic low dose of LPS pretreatment protected kidney against I/R injury. LPS treatment increased the activity and expression of iNOS, but not eNOS, in kidney tissue. LPS pretreatment in iNOS, but not eNOS, knock-out mice did not protect kidney against I/R injury. In conclusion, the kidney tolerance to I/R injury conferred by pretreatment with LPS is mediated by increased expression and activation of iNOS. [BMB reports 2010; 43(9): 629-634]

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“…Prolonged relaxation to ONOO Ϫ is likely to occur when it reacts with tissue sulfhydryls to form nitrosothiols, which can serve as NO donors, stimulating guanylate cyclase in vascular smooth muscle (26,67). Vasodilatory responses to ONOO Ϫ in coronary, pulmonary, and systemic vascular beds are inhibitible by NO scavengers and blockers of guanulate cyclase, suggesting that relaxation to ONOO Ϫ is mediated by NO or NO donors (6,24,40,41,44,63). Our novel findings support the idea that endothelium-dependent vasodilators activate a signaling pathway in which O 2 Ϫ and NO combine to produce ONOO Ϫ (Fig.…”

Section: Duction Of H 2 O 2 and Ohmentioning

confidence: 99%

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Sindler

Reyes

Chen

et al. 2013

Journal of Applied Physiology

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Sindler AL, Reyes R, Chen B, Ghosh P, Gurovich AN, Kang LS, Cardounel AJ, Delp MD, Muller-Delp JM. Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles. J Appl Physiol 114: [681][682][683][684][685][686][687][688][689][690][691][692][693] 2013. First published January 3, 2013; doi:10.1152/japplphysiol.00341.2012.-Exercise training ameliorates age-related impairments in endotheliumdependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise traininginduced enhancement of endothelial function occurs, in part, through an increase in ROS signaling. hydrogen peroxide; superoxide; peroxynitrite; nitric oxide; acetylcholine ENDOTHELIAL FUNCTION IN THE skeletal muscle resistance vasculature declines with age primarily due to decreased nitric oxide (NO) bioavailability (10,38,51,55). In feed arteries from soleus muscle, reductions in NO-dependent vasodilation are accompanied by reduced expression of endothelial NO synthase (eNOS) (65). In contrast, our laboratory has previously reported that NO-mediated vasodilation of soleus muscle arterioles declines with advancing age, despite an increase in eNOS protein levels (51). Thus the age-related decline in bioavailability of NO may be dependent on numerous other factors that regulate both NO production and degradation. eNOS activity, and subsequent NO production, is regulated by availability of substrate and cofactors, by protein-...

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Potential Benefits of Peroxynitrite

Cited by 15 publications

References 257 publications

Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice

Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice

Endotoxin-induced renal tolerance against ischemia and reperfusion injury is removed by iNOS, but not eNOS, gene-deletion

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

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