The evolutionary origins of peroxynitrite signalling

Miles, Jennifer A.; Egan, Joseph L.; Fowler, Jake A.; Machattou, Petrina; Millard, Andrew; Perry, Campbell; Scanlan, David J.; Taylor, Paul C.

doi:10.1016/j.bbrc.2021.09.071

Cited by 5 publications

(3 citation statements)

References 26 publications

(30 reference statements)

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“…Secondly, the content of NO is also decreased due to its oxidation by the superoxide anion (O 2 − ) to peroxynitrite (ONOO − ) ( 40 ). Lastly, the nitrosylation of proteins caused by the peroxynitrite in turn inhibits the activities of antioxidant enzymes and endothelial nitric oxide synthase, thus forming a vicious cycle among the condition of hyperglycemia ( 41 ). These studies provided the potential mechanisms for the association of higher urinary nitrate with lower risks of congestive heart failure and diabetic nephropathy, and the lower mortality from all causes, CVD, and diabetes documented in this study.…”

Section: Discussionmentioning

confidence: 99%

Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia

Jiang

Zhang

Yang

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Background The hyperglycemia condition disrupts the metabolism of nitrate/nitrite and nitric oxide, and dietary nitrate intake can restore nitric oxide homeostasis. This study aims to examine whether urinary nitrate is associated with diabetes complications and long-term survival among people with hyperglycemia. Methods A total of 6208 people with hyperglycemia who participated in the National Health and Nutrition Examination Survey from 2005 to 2014 were enrolled. Diabetes complications included congestive heart failure, coronary heart disease, angina, stroke, myocardial infarction, diabetic retinopathy, and nephropathy. Mortality wasobtained from the National Death Index until 2015. Urinary nitrate was measured by ion chromatography coupled with electrospray tandem mass spectrometry, which was log-transformed and categized into tertiles. Logistic regression models and cox proportional hazards models were respectively performed to assess the association of urinary nitrate with the risk of diabetes complications and disease-specific mortalities. Results After adjustment for potential confounders including urinary perchlorate and thiocyanate, compared with the participants in the lowest tertile of nitrate, the participants in the highest tertile had lower risks of congestive heart failure(odd-ratio[OR] = 0.41, 95%CI:0.27-0.60) and diabetic nephropathy(OR = 0.50, 95%CI: 0.41-0.62). Meanwhile, during a total follow-up of 41,463 person-year, the participants in the highest tertile had lower mortality risk of all-cause(hazard-ratio[HR] = 0.78, 95%CI:0.62-0.97), cardiovascular disease(CVD)(HR = 0.56, 95%CI:0.37-0.84) and diabetes(HR = 0.47, 95%CI:0.24-0.90), which showed dose-dependent linear relationships(P for non-linearity > 0.05). Moreover, no association between nitrate and cancer mortality was observed(HR = 1.13, 95%CI:0.71-1.80). Conclusions Higher urinary nitrate is associated with lower risk of congestive heart failure and diabetic nephropathy, and lower risk of all-cause, CVD, and diabetes mortalities. These findings indicated that inorganic nitrate supplementation can be considered as a supplementary treatment for people with hyperglycemia.

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Section: Discussionmentioning

confidence: 99%

Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia

Jiang

Zhang

Yang

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…In an evolutionary context, it is reasonable to think that, in higher eukaryotes, mNOS evolved from simpler single-domain bacterial homologs, acquiring a more specialized functioning with a complex multidomain protein regulated by a specific reductase and CaM-binding domains. Furthermore, there is additional evidence that NOS evolution has been influenced by horizontal gene transfer [69][70][71][72]. Respiratory complexes are well known to be targets for NO binding.…”

Section: Biological No Synthesis Via No Synthasesmentioning

confidence: 99%

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

et al. 2022

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Nitric oxide was once considered to be of marginal interest to the biological sciences and medicine; however, there is now wide recognition, but not yet a comprehensive understanding, of its functions and effects. NO is a reactive, toxic free radical with numerous biological targets, especially metal ions. However, NO and its reaction products also play key roles as reductant and oxidant in biological redox processes, in signal transduction, immunity and infection, as well as other roles. Consequently, it can be sensed, metabolized and modified in biological systems. Here, we present a brief overview of the chemistry and biology of NO—in particular, its origins in geological time and in contemporary biology, its toxic consequences and its critical biological functions. Given that NO, with its intrinsic reactivity, appeared in the early Earth’s atmosphere before the evolution of complex lifeforms, we speculate that the potential for toxicity preceded biological function. To examine this hypothesis, we consider the nature of non-biological and biological targets of NO, the evolution of biological mechanisms for NO detoxification, and how living organisms generate this multifunctional gas.

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“…These reactive molecules can also react together and create new reactive signalling molecules. Superoxide and NO can react, for example, to create peroxynitrite, a signalling molecule in its own right [ 20 ]. NO and H 2 S will react to generate nitrosothiols [ 21 ], which can also act in a signalling role.…”

Section: Introductionmentioning

confidence: 99%

Are Protein Cavities and Pockets Commonly Used by Redox Active Signalling Molecules?

Hancock

2023

Plants

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It has been well known for a long time that inert gases, such as xenon (Xe), have significant biological effects. As these atoms are extremely unlikely to partake in direct chemical reactions with biomolecules such as proteins, lipids, and nucleic acids, there must be some other mode of action to account for the effects reported. It has been shown that the topology of proteins allows for cavities and hydrophobic pockets, and it is via an interaction with such protein structures that inert gases are thought to have their action. Recently, it has been mooted that the relatively inert gas molecular hydrogen (H2) may also have its effects via such a mechanism, influencing protein structures and actions. H2 is thought to also act via interaction with redox active compounds, particularly the hydroxyl radical (·OH) and peroxynitrite (ONOO−), but not nitric oxide (NO·), superoxide anions (O2·−) or hydrogen peroxide (H2O2). However, instead of having a direct interaction with H2, is there any evidence that these redox compounds can also interact with Xe pockets and cavities in proteins, either having an independent effect on proteins or interfering with the action of inert gases? This suggestion will be explored here.

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The evolutionary origins of peroxynitrite signalling

Cited by 5 publications

References 26 publications

Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia

Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia

The Evolution of Nitric Oxide Function: From Reactivity in the Prebiotic Earth to Examples of Biological Roles and Therapeutic Applications

Are Protein Cavities and Pockets Commonly Used by Redox Active Signalling Molecules?

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