Cyclic GMP and Nitric Oxide Synthase in Aging and Alzheimer's Disease

Domek-Łopacińska, K.; Strosznajder, Joanna B.

doi:10.1007/s12035-010-8104-x

Cited by 112 publications

(91 citation statements)

References 61 publications

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“…Finally, we cannot rule out that an increase in phosphodiesterase (PDE) activity as responsible for the decrease in cyclic GMP content. In fact, aging process has been associated with an increase in PDE expression and activity and a decrease in cyclic GMP concentration (for review, see Domek-Łopacińska and Strosznajder 2010). This notion is in agreement with data indicating that inhibitors of PDE2 and PDE9 improve learning and memory in older rats (van der Staay et al 2008) as well as in rat model of hepatic encephalopathy Cauli et al 2010).…”

Section: Discussionsupporting

confidence: 70%

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

Kawamoto

Vasconcelos

Degaspari

et al. 2012

AGE

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Aging is associated with an increased susceptibility to neurodegenerative disorders which has been linked to chronic inflammation. This process generates oxygen-reactive species, ultimately responsible for a process known as oxidative stress, leading to changes in nitric oxide (NO), and cyclic guanosine monophosphate (cyclic GMP) signaling pathway. In previous studies, we showed that human aging was associated with an increase in NO Synthase (NOS) activity, a decrease in basal cyclic GMP levels in human platelets, and an increase in thiobarbituric acid-reactant substances (TBARS) in erythrocytes. The aim of the present work was to evaluate NOS activity, TBARS and cyclic GMP levels in hippocampus and frontal cortex and its correlation to platelets and erythrocytes of 4-, 12-, and 24-month-old rats. The result showed an age-related decrease in cyclic GMP levels which was linked to an increase in NOS activity and TBARS in both central areas as well as in platelets and erythrocytes of rats. The present data confirmed our previous studies performed in human platelets and erythrocytes and validate NOS activity and cyclic GMP in human platelet as well as TBARS in erythrocytes as biomarkers to study agerelated disorders and new anti-aging therapies.

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Section: Discussionsupporting

confidence: 70%

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

Kawamoto

Vasconcelos

Degaspari

et al. 2012

AGE

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“…However, it is well known that the capacity of vascular endothelium to generate nitric oxide (NO) declines with aging, even in healthy individuals. Thus, endothelial function was persistently impaired with increasing age, through accelerated nitric oxide (NO) degradation [37], reduced endothelial nitric oxide synthase (eNOS) expression/action [38], increased production of reactive oxygen species [39], inhibition of NOS activity by endogenous NOS inhibitors, inflammatory reactions [39], and increased phosphodiesterase activity [40], decreased endothelial progenitor cells [41]. Anyway, UA was produced by a series of enzymatic waterfall-like reaction by which NADPH was a main intermediate by-product.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Uric Acid and Endothelial Function in Hypertensive Patients with Metabolic Syndrome

Huang¹,

Cai²,

Zheng³

et al. 2016

J Clin Exp Cardiolog

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Aim: To investigate the association between uric acid (UA) and endothelial function in Chinese hypertensive patients with Metabolic Syndrome (MS).Methods: 615 hypertensive patients were enrolled, all hypertensives were divided into two groups: hypertensives with MS (MS group, n=239) and hypertensives without MS (NMS group, n=376). 87 age-and sex-matched normotensives served as controls (NC group). Flow-mediated (endothelium-dependent) dilatations (FMD), nitroglycerin-induced (endothelium-independent) dilatation (EID) in the brachial artery were assessed by highresolution ultrasonography. UA was detected by urease indophenol. .58)%, p<0.001) among groups. After stratification of gender, lower FMD was only seen in male hypertensives with MS accompanied by hyperuricemia <60 years old ((9.98 ± 5.78)% vs (7.12 ± 4.49)%, p<0.05); Pearson correlation analysis showed that the FMD was negatively correlated with UA (r=-0.314, p<0.01); Finally, logistic regression analysis showed that a 50 µmol/L increase in UA levels carried a 41.1% higher risk for endothelial dysfunction in this cohort. Conclusions: A higher UA level is related to poorer endothelial function in hypertensives with MS. Increased UA can be used as an alternative indicator for monitoring endothelial function and preventing vascular damage in male hypertensives with MS aged less than 60 years old.Keywords: Uric acid; Endothelial dysfunction; Hypertension; Metabolic syndrome InstructionRecently, several studies have indicated that uric acid (UA), the circulating end-metabolite of purine nucleotides of mankind, is associated with subsequent cardiovascular diseases [1,2]. However, it remains controversial whether UA is a relevant and independent risk factor for cardiovascular disease and the mechanisms by which UA results in target organ injury are still unknown. Increasing data suggest that UA is associated with endothelial dysfunction [3,4], which is characteristic of patients with essential hypertension [5]. It is well recognized that endothelial dysfunction is an early stage in atherogenesis and associates with poor cerebro-cardiovascular outcomes [6]. It has been shown that UA disturbs endothelial function by disrupting nitric oxide (NO) synthesis, inhibiting NO bioavailability and activating the renin-angiotensin system.Metabolic syndrome (MS) is believed to be a clustering of abnormalities of several cardiovascular risk factors in an individual including abdominal obesity, hypertension, and dyslipidemia, including low HDL-C, high LDL-C and hyperglycemia. MS is often associated with elevated UA levels [7] and endothelial dysfunction [8,9]. The prevalence of MS has been increasing in recent years in China. A recent epidemiological study showed that the prevalence of MS among Chinese men and women aged 35 to 64 years old was 9.8% and 17.8%, respectively [10]. As is known to all, MS is quite common in patients with primary hypertension and carries much higher risk of cardiovascular events. It was reported that nearly 90% of Chinese hypertensives were ...

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“…sGC, the physiological NO receptor, catalyzes the conversion of guanosine-5 0 -triphosphate (GTP) to the secondary messenger guanosine-3,5-cyclic monophosphate (cGMP), which in turn plays a pivotal role in several physiological processes including vasodilatation and neuronal signal transduction [77][78][79][80][81][82][83][84] (Fig. 1).…”

Section: Co Signalingmentioning

confidence: 99%

CO metabolism, sensing, and signaling

et al. 2011

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Abstract.CO is a colorless and odorless gas produced by the incomplete combustion of hydrocarbons, both of natural and anthropogenic origin. Several microorganisms, including aerobic and anaerobic bacteria and anaerobic archaea, use exogenous CO as a source of carbon and energy for growth. On the other hand, eukaryotic organisms use endogenous CO, produced during heme degradation, as a neurotransmitter and as a signal molecule. CO sensors act as signal transducers by coupling a ''regulatory'' heme-binding domain to a ''functional'' signal transmitter. Although high CO concentrations inhibit generally heme-protein actions, low CO levels can influence several signaling pathways, including those regulated by soluble guanylate cyclase and/or mitogenactivated protein kinases. This review summarizes recent insights into CO metabolism, sensing, and signaling.

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Cyclic GMP and Nitric Oxide Synthase in Aging and Alzheimer's Disease

Cited by 112 publications

References 61 publications

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system

Relationship between Uric Acid and Endothelial Function in Hypertensive Patients with Metabolic Syndrome

CO metabolism, sensing, and signaling

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