5.2 Nitric Oxide in Regulation of Mitochondrial Function, Respiration, and Glycolysis

Bolaños, Juan P.; Almeida, Ángeles

doi:10.1007/978-0-387-30411-3_18

Cited by 3 publications

(3 citation statements)

References 237 publications

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“…Free radicals (compounds with an unpaired electron) or ROS are a normal part of metabolism. As part of their role in normal metabolism, ROS serve as signaling molecules [132]. ROS communicate between metabolic pathways and have been shown to modify neurotransmitter receptors and ion transporters [133].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Sequence Variation Associated with Dementia and Cognitive Function in the Elderly

Tranah

Nalls

Katzman

et al. 2012

JAD

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Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increased neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10–12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia (OR = 1.86, 95% CI = 1.23, 2.82, p = 0.0008) and haplogroup J participants experienced a statistically significant 8-year decline in 3MS (β = −0.14, 95% CI = −0.27, −0.03, p = 0.0006), both compared with common haplogroup H. The m.15244A>G, p.G166G, CytB variant was associated with a significant decline in DSST score (β = −0.58, 95% CI −0.89, −0.28, p = 0.00019) and the m.14178T>C, p.I166V, ND6 variant was associated with a significant decline in 3MS score (β = −0.87, 95% CI −1.31, −3.86, p = 0.00012). Finally, we sequenced the complete ∼16.5 kb mtDNA from 135 Health ABC participants and identified several highly conserved and potentially functional nonsynonymous variants unique to 22 dementia cases and aggregate sequence variation across the hypervariable 2-3 regions that influences 3MS and DSST scores.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Sequence Variation Associated with Dementia and Cognitive Function in the Elderly

Tranah

Nalls

Katzman

et al. 2012

JAD

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“…NO has great impact on energy metabolism [163,164]. NO increases the energy substrates and oxygen availability to cells and tissues by increasing blood flow.…”

Section: Nitric Oxide and Cancer Metabolismmentioning

confidence: 99%

Cancer cell metabolism and the modulating effects of nitric oxide

Chang

Diers

Hogg

2015

Free Radical Biology and Medicine

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Altered metabolic phenotype has been recognized as a hallmark of tumor cells for many years, but this aspect of the cancer phenotype has come into greater focus in recent years. NOS2 (inducible nitric oxide synthase of iNOS) has been implicated as a component in many aggressive tumor phenotypes, including melanoma, glioblastoma and breast cancer. Nitric oxide has been well established as a modulator of cellular bioenergetics pathways, in many ways similar to the alteration of cellular metabolism observed in aggressive tumors. In this review we attempt to bring these concepts together with the general hypothesis that one function of NOS2 and NO in cancer is to modulate metabolic processes to facilitate increased tumor aggression. There are many mechanisms by which NO can modulate tumor metabolism, including direct inhibition of respiration, alterations in mitochondrial mass, oxidative inhibition of bioenergetic enzymes, and the stimulation of secondary signaling pathways. Here we review metabolic alterations in the context of cancer cells and discuss the role of NO as a potential mediator of these changes.

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“…Many physiological reactions in all tissues including the ETC are modulated by NO• [6]. ROS can modify neurotransmitter receptors or ion transporters with profound effect on the function of these proteins [1].…”

Section: Introductionmentioning

confidence: 99%

A Mitocentric View of Alzheimer's Disease Suggests Multi-Faceted Treatments

Gibson

Shi

2010

JAD

105

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Alzheimer’s disease (AD) is defined by plaques made of amyloid-β peptide (Aβ), tangles made of hyper-phosphorylated tau proteins and memory deficits. Thus, the events initiating the cascade leading to these end points may be more effective therapeutic targets than treating each facet individually. In the small percentage of cases of AD that are genetic (or animal models that reflect this form of AD), the factor initiating AD is clear (e.g. genetic mutations lead to high Aβ1–42 or hyperphosphorylated tau proteins). In the vast majority of AD cases, the cause is unknown. Substantial evidence now suggests that abnormalities in Glucose metabolism/Mitochondrial function/Oxidative stress (GMO) are an invariant feature of AD and occur at early stage of the disease process in both genetic and non-genetic forms of AD. Indeed, decreases in brain glucose utilization are diagnostic for AD. Changes in calcium homeostasis also precede clinical manifestations of AD. Abnormal GMO can lead to plaques, tangles and the calcium abnormalities that accompany AD. Abnormalities in GMO diminish the ability of the brain to adapt. Therapies targeting mitochondria may ameliorate abnormalities in plaques, tangles, calcium homeostasis and cognition that comprise AD.

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5.2 Nitric Oxide in Regulation of Mitochondrial Function, Respiration, and Glycolysis

Cited by 3 publications

References 237 publications

Mitochondrial DNA Sequence Variation Associated with Dementia and Cognitive Function in the Elderly

Mitochondrial DNA Sequence Variation Associated with Dementia and Cognitive Function in the Elderly

Cancer cell metabolism and the modulating effects of nitric oxide

A Mitocentric View of Alzheimer's Disease Suggests Multi-Faceted Treatments

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