Dataset Information

Redox Post-translational Modifications of Protein Thiols in Brain Aging and Neurodegenerative Conditions-Focus on S-Nitrosation.

ABSTRACT: Reactive oxygen species and reactive nitrogen species (RONS) are by-products of aerobic metabolism. RONS trigger a signaling cascade that can be transduced through oxidation-reduction (redox)-based post-translational modifications (redox PTMs) of protein thiols. This redox signaling is essential for normal cellular physiology and coordinately regulates the function of redox-sensitive proteins. It plays a particularly important role in the brain, which is a major producer of RONS. Aberrant redox PTMs of protein thiols can impair protein function and are associated with several diseases. This mini review article aims to evaluate the role of redox PTMs of protein thiols, in particular S-nitrosation, in brain aging, and in neurodegenerative diseases. It also discusses the potential of using redox-based therapeutic approaches for neurodegenerative conditions.

SUBMITTER: Finelli MJ

PROVIDER: S-EPMC7497228 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Redox Post-translational Modifications of Protein Thiols in Brain Aging and Neurodegenerative Conditions-Focus on S-Nitrosation.

Finelli Mattéa J MJ

Frontiers in aging neuroscience 20200903

Reactive oxygen species and reactive nitrogen species (RONS) are by-products of aerobic metabolism. RONS trigger a signaling cascade that can be transduced through oxidation-reduction (redox)-based post-translational modifications (redox PTMs) of protein thiols. This redox signaling is essential for normal cellular physiology and coordinately regulates the function of redox-sensitive proteins. It plays a particularly important role in the brain, which is a major producer of RONS. Aberrant redox ...[more]

PMID: 33088270

Similar Datasets

Project description:The impact of climate change entails a progressive and inexorable modification of the Earth's climate and events such as salinity, drought, extreme temperatures, high luminous intensity and ultraviolet radiation tend to be more numerous and prolonged in time. Plants face their exposure to these abiotic stresses or their combination through multiple physiological, metabolic and molecular mechanisms, to achieve the long-awaited acclimatization to these extreme conditions, and to thereby increase their survival rate. In recent decades, the increase in the intensity and duration of these climatological events have intensified research into the mechanisms behind plant tolerance to them, with great advances in this field. Among these mechanisms, the overproduction of molecular reactive species stands out, mainly reactive oxygen, nitrogen and sulfur species. These molecules have a dual activity, as they participate in signaling processes under physiological conditions, but, under stress conditions, their production increases, interacting with each other and modifying and-or damaging the main cellular components: lipids, carbohydrates, nucleic acids and proteins. The latter have amino acids in their sequence that are susceptible to post-translational modifications, both reversible and irreversible, through the different reactive species generated by abiotic stresses (redox-based PTMs). Some research suggests that this process does not occur randomly, but that the modification of critical residues in enzymes modulates their biological activity, being able to enhance or inhibit complete metabolic pathways in the process of acclimatization and tolerance to the exposure to the different abiotic stresses. Given the importance of these PTMs-based regulation mechanisms in the acclimatization processes of plants, the present review gathers the knowledge generated in recent years on this subject, delving into the PTMs of the redox-regulated enzymes of plant metabolism, and those that participate in the main stress-related pathways, such as oxidative metabolism, primary metabolism, cell signaling events, and photosynthetic metabolism. The aim is to unify the existing information thus far obtained to shed light on possible fields of future research in the search for the resilience of plants to climate change.

Project description:Preterm infants and patients with lung disease often have excess fluid in the lungs and are frequently treated with oxygen, however long-term exposure to hyperoxia results in irreversible lung injury. Although the adverse effects of hyperoxia are mediated by reactive oxygen species, the full extent of the impact of hyperoxia on redox-dependent regulation in the lung is unclear. In this study, neonatal mice overexpressing the beta-subunit of the epithelial sodium channel (β-ENaC) encoded by Scnn1b and their wild type (WT; C57Bl6) littermates were utilized to study the pathogenesis of high fraction inspired oxygen (FiO2)-induced lung injury. Results showed that O2-induced lung injury in transgenic Scnn1b mice is attenuated following chronic O2 exposure. To test the hypothesis that reversible cysteine-redox-modifications of proteins play an important role in O2-induced lung injury, we performed proteome-wide profiling of protein S-glutathionylation (SSG) in both WT and Scnn1b overexpressing mice maintained at 21% O2 (normoxia) or FiO2 85% (hyperoxia) from birth to 11-15 days postnatal. Over 7700 unique Cys sites with SSG modifications were identified and quantified, covering more than 3000 proteins in the lung. In both mouse models, hyperoxia resulted in a significant alteration of the SSG levels of Cys sites belonging to a diverse range of proteins. In addition, substantial SSG changes were observed in the Scnn1b overexpressing mice exposed to hyperoxia, suggesting that ENaC plays a critically important role in cellular regulation. Hyperoxia-induced SSG changes were further supported by the results observed for thiol total oxidation, the overall level of reversible oxidation on protein cysteine residues. Differential analyses reveal that Scnn1b overexpression may protect against hyperoxia-induced lung injury via modulation of specific processes such as cell adhesion, blood coagulation, and proteolysis. This study provides a landscape view of protein oxidation in the lung and highlights the importance of redox regulation in O2-induced lung injury.

Project description:Post-translational modifications (PTMs) have been confirmed to be involved in multiple female reproductive events, but their role in physiological ovarian aging is far from elucidated. In this study, mice aged 3, 12 or 17 months (3M, 12M, 17M) were selected as physiological ovarian aging models. The expression of female reproductive function-related genes, the global profiles of PTMs, and the level of histone modifications and related regulatory enzymes were examined during physiological ovarian aging in the mice by quantitative real-time PCR and western blot, respectively. The results showed that the global protein expression of Kbhb (lysineβ-hydroxybutyryllysine), Khib (lysine 2-hydroxyisobutyryllysine), Kglu (lysineglutaryllysine), Kmal (lysinemalonyllysine), Ksucc (lysinesuccinyllysine), Kcr (lysinecrotonyllysine), Kbu (lysinebutyryllysine), Kpr (lysinepropionyllysine), SUMO1 (SUMO1 modification), ub (ubiquitination), P-Typ (phosphorylation), and 3-nitro-Tyr (nitro-tyrosine) increased significantly as mice aged. Moreover, the modification level of Kme2 (lysinedi-methyllysine) and Kac (lysineacetyllysine) was the highest in the 3M mice and the lowest in 12M mice. In addition, only trimethylation of histone lysine was up-regulated progressively and significantly with increasing age (p < 0.001), H4 ubiquitination was obviously higher in the 12M and 17M mice than 3M (p < 0.001), whereas the modification of Kpr (lysinepropionylation) and O-GlcNA in 17M was significantly decreased compared with the level in 3M mice (p < 0.05, p < 0.01). Furthermore, the expression levels of the TIP60, P300, PRDM9, KMT5B, and KMT5C genes encoding PTM regulators were up-regulated in 17M compared to 3M female mice (p < 0.05). These findings indicate that altered related regulatory enzymes and PTMs are associated with physiological ovarian aging in mice, which is expected to provide useful insights for the delay of ovarian aging and the diagnosis and treatment of female infertility.

Dataset Information

Redox Post-translational Modifications of Protein Thiols in Brain Aging and Neurodegenerative Conditions-Focus on S-Nitrosation.

Publications

Redox Post-translational Modifications of Protein Thiols in Brain Aging and Neurodegenerative Conditions-Focus on S-Nitrosation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets