Enhanced Peroxynitrite Formation Is Associated with Vascular Aging

Loo, Bernd van der; Labugger, Ralf; Skepper, Jeremy N.; Bachschmid, Markus; Kilo, Juliane; Powell, Janet M.; Palacios-Callender, Miriam; Erusalimsky, Jorge D.; Quaschning, Thomas; Maliński, Tadeusz; Gygi, Daniel; Ullrich, Volker; Lüscher, Thomas F.

doi:10.1084/jem.192.12.1731

Cited by 609 publications

(529 citation statements)

References 43 publications

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“…This assumption was indirectly supported by our finding of tyrosine-nitrated mitochondrial Mn-SOD in these aged rats (van der Loo et al, 2000), which suggests the formation of mitochondrial derived PN and hence probably mitochondrial • O 2 -as a primary reactant. A more direct proof for the source of • O 2 -remains a challenge for future research.…”

Section: Discussionsupporting

confidence: 57%

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Superoxide as a Messenger of Endothelial Function

Ullrich

Bachschmid²

2000

Biochemical and Biophysical Research Communications

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Section: Discussionsupporting

confidence: 57%

“…In agreement with the "oxidative stress hypothesis" of aging, a markedly increased • O 2 -production followed by NO conversion to PN occurring with aging has been shown (van der Loo et al, 2000). However, the molecular mechanisms responsible for this age-dependent increased formation of • O 2 -remain obscure.…”

Section: Introductionsupporting

confidence: 62%

Superoxide as a Messenger of Endothelial Function

Ullrich

Bachschmid²

2000

Biochemical and Biophysical Research Communications

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“…Although little is known about the effects of nitration of tyrosines on the in vivo function of proteins 12 , peroxynitrite and its decomposition products induce peroxidation of the membrane lipids 13 and may initiate lipid peroxidation of human LDL 14 , causing endothelial lesions and an increase in vascular permeability 10 . Several studies indicate that the endothelium-dependent deficiency in vascular relaxation is associated with inactivation of nitric oxide by formation of peroxynitrite [15][16][17] .…”

Section: Lipid Peroxidation and Nitric Oxide Inactivation In Postmenomentioning

confidence: 99%

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Pereira

Bertolami

Faludi

et al. 2003

Arq. Bras. Cardiol.

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Original ArticleCardiovascular diseases are less prevalent in premenopausal women and in those receiving hormone replacement therapy as compared with postmenopausal women and men 1 . This protective effect is attributed to estrogens, and one of the mechanisms of action may be related to the metabolism of plasma lipoproteins 2 .Estrogens reduce LDL-cholesterol and increase HDLcholesterol 3 . However, these changes in lipid profile only contribute to approximately 25% of the protective effect of estrogens 4 . Other potential mechanisms of action of estrogens may include protection against LDL oxidation 5 , reduction in lipoprotein(a), potentiation of fibrinolysis 6 , and increase in insulin sensitivity. In the arteries, estrogens improve vasodilating function, decrease calcification, secretion of cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and formation of atherosclerotic lesions 7 .Direct action of estrogens on the arterial wall has also been demonstrated. The administration of estrogens for prolonged periods inhibits the deposition of cholesterol in the arteries and thickening of the intima in monkeys and rabbits fed an atherogenic diet 8 . However, the mechanisms determining the direct effects of estrogens on the arterial wall have not been completely elucidated. The hemodynamic effects may be partially measured by the activity of estrogens on the synthesis of endothelial nitric oxide 9 . Estrogens have been suggested to possibly improve endothelial function and decrease the risks of atherosclerosis in premenopausal women. Nitric oxide has its bioactivity reduced in postmenopausal women. However, it is not clear whether this occurs due to its lower production by nitric oxide synthase, or whether nitric oxide is inactivated by reaction with the superoxide radical also generated by endothelial cells, forming the peroxynitrite anion (ONOO -), which is a strong oxidizing agent.Peroxynitrite is decomposed into other reactive oxygen species ( fig. 1) 10 and reacts with tyrosine residues of proteins to form nitrotyrosine 11 . Although little is known NOx, nitrotyrosine, COx, CE 18:2 -OOH, and PC-OOH were higher in the postmenopausal period (33.8±22.3 µM; 230±130 nM; 55±19 ng/µL; 17±8.7 nM; 2775±460 nM, respectively) Objective -To assess the effect of endogenous estrogens on the bioavailability of nitric oxide (·NO) and in the formation of lipid peroxidation products in pre-and postmenopausal women. Methods -NOx and S-nitrosothiols were determined by gaseous phase chemiluminescence, nitrotyrosine was determined by ELISA, COx (cholesterol oxides) by gas chromatography, and cholesteryl linoleate hydroperoxides (CE 18:2 -OOH), trilinolein (TG 18:2 -OOH), and phospholipids (PC-OOH) by HPLC in samples of plasma. Results -The concentrations of

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“…The contribution of NO pathway for vascular aging is far from being consensual, as it was reported a reduction on eNOS mRNA levels (Challah et al 1997) and contrariwise, an increase of eNOS enzyme expression combined with reduced activity (Cernadas et al 1998) in aged animals. Nevertheless, eNOS could be overactivated, mainly through Akt-mediated phosphorylation (Lovren et al 2009), as a compensatory mechanism to counterbalance endothelial dysfunction induced by agedependent oxidative stress (van der Loo et al 2000).…”

mentioning

confidence: 99%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

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Enhanced Peroxynitrite Formation Is Associated with Vascular Aging

Cited by 609 publications

References 43 publications

Superoxide as a Messenger of Endothelial Function

Superoxide as a Messenger of Endothelial Function

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

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