Dataset Information

Features of Oxidative and Nitrosative Metabolism in Lung Diseases.

ABSTRACT: Respiratory diseases are accompanied by intensification of free radical processes at different levels of the biological body organization. Simultaneous stress and suppression of various parts of antioxidant protection lead to the development of oxidative stress (OS) and nitrosative stress (NS). The basic mechanisms of initiation and development of the OS and NS in pulmonary pathology are considered. The antioxidant defense system of the respiratory tract is characterized. The results of the NS and OS marker study in various respiratory diseases are presented. It is shown that NS and OS are multilevel complex-regulated processes, existing and developing in inseparable connection with a number of physiological and pathophysiological processes. The study of NS and OS mechanisms contributes to the improvement of the quality of diagnosis and the development of therapeutic agents that act on different pathogenetic stages of the disease.

SUBMITTER: Soodaeva S

PROVIDER: S-EPMC6556356 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Features of Oxidative and Nitrosative Metabolism in Lung Diseases.

Soodaeva Svetlana S Kubysheva Nailya N Klimanov Igor I Nikitina Lidiya L Batyrshin Ildar I

Oxidative medicine and cellular longevity 20190522

Respiratory diseases are accompanied by intensification of free radical processes at different levels of the biological body organization. Simultaneous stress and suppression of various parts of antioxidant protection lead to the development of oxidative stress (OS) and nitrosative stress (NS). The basic mechanisms of initiation and development of the OS and NS in pulmonary pathology are considered. The antioxidant defense system of the respiratory tract is characterized. The results of the NS a ...[more]

PMID: 31249640

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Project description:BackgroundIt is well established that both cerebral hypoperfusion/stroke and type 2 diabetes are risk factors for Alzheimer's disease (AD). Recently, the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has begun to be established. However, the role of the key common denominator, namely nitric oxide (NO), in AD is largely unknown. In this study, we investigated redox regulation of BACE1, the rate-limiting enzyme responsible for the ?-cleavage of APP to A? peptides.ResultsHerein, we studied events such as S-nitrosylation, a covalent modification of cysteine residues by NO, and H2O2-mediated oxidation. We found that NO and H2O2 differentially modulate BACE1 expression and enzymatic activity: NO at low concentrations (<100 nM) suppresses BACE1 transcription as well as its enzymatic activity while at higher levels (0.1-100 ?M) NO induces S-nitrosylation of BACE1 which inactivates the enzyme without altering its expression. Moreover, the suppressive effect on BACE1 transcription is mediated by the NO/cGMP-PKG signaling, likely through activated PGC-1?. H2O2 (1-10 ?M) induces BACE1 expression via transcriptional activation, resulting in increased enzymatic activity. The differential effects of NO and H2O2 on BACE1 expression and activity are also reflected in their opposing effects on A? generation in cultured neurons in a dose-dependent manner. Furthermore, we found that BACE1 is highly S-nitrosylated in normal aging brains while S-nitrosylation is markedly reduced in AD brains.ConclusionThis study demonstrates for the first time that BACE1 is highly modified by NO via multiple mechanisms: low and high levels of NO suppress BACE1 via transcriptional and post translational regulation, in contrast with the upregulation of BACE1 by H2O2-mediated oxidation. These novel NO-mediated regulatory mechanisms likely protect BACE1 from being further oxidized by excessive oxidative stress, as from H2O2 and peroxynitrite which are known to upregulate BACE1 and activate the enzyme, resulting in excessive cleavage of APP and A? generation; they likely represent the crucial house-keeping mechanism for BACE1 expression/activation under physiological conditions.

Dataset Information

Features of Oxidative and Nitrosative Metabolism in Lung Diseases.

Publications

Features of Oxidative and Nitrosative Metabolism in Lung Diseases.

Similar Datasets

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