Sirtuins: Enzymes with multidirectional catalytic activity

Sirtuins (SIRT) are NAD+-dependent histone deacetylases that play an important role in the functioning of the human body. They participate in numerous processes taking place in cells, including in the post-translational modification of proteins, silencing gene transcription, inducing repair processes, as well as in the regulation of metabolic processes. Sirtuins have also been shown to play an important role in reducing the level of reactive oxygen species as well as in stimulating cell growth, aging and death. Such a wide range of processes, which are affected by sirtuins, have recently made sirtuins the object of many studies aimed at a detailed understanding of the mechanisms of their action and the role they play. The aim of our study was to collect and systematize information on sirtuins, mainly from the last 10 years, both regarding the human body and based on the results of research on animal models or cell lines. The article discusses the structure, function and biological role of sirtuins in cellular processes.

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The Involvement of Reactive Oxygen Species in Polyploidization of the M-07e Human Megakaryocytic Cell Line.

Blood ◽

10.1182/blood.v106.11.4300.4300 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4300-4300

Author(s):

Serge Côté ◽

Nathalie Dussault ◽

Carl Simard

Keyword(s):

Reactive Oxygen Species ◽

Cell Line ◽

Reactive Oxygen ◽

Cell Types ◽

Oxygen Species ◽

Botulin Toxin ◽

Cellular Processes ◽

Intracellular Ros ◽

Wide Range ◽

Megakaryocytic Cell

Abstract Hematopoietic cells mature in the bone marrow under the control of a diversity of growth factors and the influence of various cell types producing superoxide and other reactive oxygen species (ROS). As ROS may regulate activities of redox-sensitive enzymes implicated in a wide range of cellular processes, we have exposed the human megakaryocytic cell line M-07e to hydrogen peroxide (H2O2) at concentrations that increased intracellular ROS and examined whether expression of the megakaryocytic programme could be enhanced. The growth-factor dependent M-07e cells display surface markers characteristic of both early myeloid progenitors and more committed members of the magakaryocyte (Mk) lineage, such as glycoproteins GPIIb-IIIa (CD41) and GPIb (CD42). H2O2 significantly reduced cell proliferation without affecting viability. After 4 days of exposure to this reagent, expression of the early Mk marker CD41 was 1.2 times higher than that of control cells. Although no change in the expression of the late Mk marker CD42 was detected, exposure to H2O2 was found to increase the incidence of multinucleate cells, polyploidy and abnormal microtubule organising centre numbers. Investigation of this phenomenon on synchronized M-07e cells revealed that H2O2 arrested cytokinesis at a late stage and that some nuclei were still able to incorporate bromodeoxyuridine (BrdU). Cell division was similarly impaired when M-07e cells were either exposed to botulin toxin C3 transferase or Y-27362 inhibitor, suggesting that H2O2 treatments affected members of the Rho family of small GTP-binding proteins and/or their effectors. Together, these findings indicate that endoreplication in Mk may be linked to changes in the cellular redox state of these cells and support the concept that differentiation and polyploidization are independently regulated events.

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Enhanced Synthesis of Poly Gamma Glutamic Acid by Increasing the Intracellular Reactive Oxygen Species in the Bacillus licheniformis Δ1-pyrroline-5-carboxylate Dehydrogenase Gene ycgN Deficient Strain

10.1101/337402 ◽

2018 ◽

Author(s):

Bichan Li ◽

Dongbo Cai ◽

Shiying Hu ◽

Anting Zhu ◽

Zhili He ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Glutamic Acid ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Oxygen Species ◽

Proline Metabolism ◽

Cellular Processes ◽

Proline Catabolism ◽

Double Mutant Strain ◽

Wide Range

AbstractPoly gamma glutamic acid (γ-PGA) is an anionic polyamide with numerous applications. Proline metabolism influences the formation of reactive oxygen species (ROS), and is involved in a wide range of cellular processes. However, the relation between proline metabolism and γ-PGA synthesis has not yet been analyzed. In this study, our results indicated that the deletion of Δ1-pyrroline-5-carboxylate dehydrogenase encoded gene ycgN resulted in 85.22% higher yield of γ-PGA in B. licheniformis WX-02. But the deletion of proline dehydrogenase encoded gene ycgM had no effect on γ-PGA synthesis. Meanwhile, a 2.92-fold higher level of P5C was detected in ycgN deficient strain WXΔycgN, while the P5C levels in WXΔycgM and double mutant strain WXΔycgMN remained the same, compared to WX-02. The ROS level of WXΔycgN was 1.18-fold higher than that of WX-02, and the addition of n-acetylcysteine (antioxidant) into medium could decrease its ROS level, further reduced the γ-PGA yield. Our results showed that proline catabolism played an important role in maintaining ROS homeostasis, and the deletion of ycgN caused P5C accumulation, which induced a transient ROS signal to promote γ-PGA synthesis in B. licheniformis.Importanceγ-PGA is an anionic polyamide with various applications in biomedical and industrial fields. Proline metabolism influences the intracellular reactive oxygen species (ROS) and is involved in a wide range of cellular processes. Here, we report the effects of proline metabolism on γ-PGA synthesis. Our results indicated that deletion of ycgN promoted the synthesis of γ-PGA by increasing the intracellular levels of Δ1-pyrroline-5-carboxylate to generate a transient ROS signal in B. licheniformis WX-02. This study provides the valuable information that enhanced synthesis of γ-PGA by knocking out of ycgN.

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Role of adaptor protein p66Shc in renal pathologies

AJP Renal Physiology ◽

10.1152/ajprenal.00414.2017 ◽

2018 ◽

Vol 314 (2) ◽

pp. F143-F153 ◽

Cited By ~ 6

Author(s):

Kevin D. Wright ◽

Alexander Staruschenko ◽

Andrey Sorokin

Keyword(s):

Reactive Oxygen Species ◽

Adaptor Protein ◽

Adaptor Proteins ◽

Review Article ◽

Oxygen Species ◽

Kidney Physiology ◽

Signaling Mechanisms ◽

Wide Range ◽

Key Questions

p66Shc is one of the three adaptor proteins encoded by the Shc1 gene, which are expressed in many organs, including the kidney. Recent studies shed new light on several key questions concerning the signaling mechanisms mediated by p66Shc. The central goal of this review article is to summarize recent findings on p66Shc and the role it plays in kidney physiology and pathology. This article provides a review of the various mechanisms whereby p66Shc has been shown to function within the kidney through a wide range of actions. The mitochondrial and cytoplasmic signaling of p66Shc, as it relates to production of reactive oxygen species (ROS) and renal pathologies, is further discussed.

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The Role of Reactive Oxygen Species in Arsenic Toxicity

Biomolecules ◽

10.3390/biom10020240 ◽

2020 ◽

Vol 10 (2) ◽

pp. 240 ◽

Cited By ~ 14

Author(s):

Yuxin Hu ◽

Jin Li ◽

Bin Lou ◽

Ruirui Wu ◽

Gang Wang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Arsenic Exposure ◽

Treatment Strategies ◽

Reactive Oxygen ◽

Cell Behavior ◽

Arsenic Toxicity ◽

Oxygen Species ◽

Wide Range ◽

Global Health Problem

Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.

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The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia

International Journal of Molecular Sciences ◽

10.3390/ijms20236003 ◽

2019 ◽

Vol 20 (23) ◽

pp. 6003 ◽

Cited By ~ 18

Author(s):

Sillar ◽

Germon ◽

DeIuliis ◽

Dun

Keyword(s):

Reactive Oxygen Species ◽

Acute Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Reactive Oxygen ◽

Clinical Work ◽

Oxygen Species ◽

Poor Overall Survival ◽

Wide Range ◽

Acute Myeloid

Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with a poor overall survival. Reactive oxygen species (ROS) have been shown to be elevated in a wide range of cancers including AML. Whilst previously thought to be mere by-products of cellular metabolism, it is now clear that ROS modulate the function of signalling proteins through oxidation of critical cysteine residues. In this way, ROS have been shown to regulate normal haematopoiesis as well as promote leukaemogenesis in AML. In addition, ROS promote genomic instability by damaging DNA, which promotes chemotherapy resistance. The source of ROS in AML appears to be derived from members of the “NOX family” of NADPH oxidases. Most studies link NOX-derived ROS to activating mutations in the Fms-like tyrosine kinase 3 (FLT3) and Ras-related C3 botulinum toxin substrate (Ras). Targeting ROS through either ROS induction or ROS inhibition provides a novel therapeutic target in AML. In this review, we summarise the role of ROS in normal haematopoiesis and in AML. We also explore the current treatments that modulate ROS levels in AML and discuss emerging drug targets based on pre-clinical work.

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Reactive Oxygen Species in Macrophages: Sources and Targets

Frontiers in Immunology ◽

10.3389/fimmu.2021.734229 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marcella Canton ◽

Ricardo Sánchez-Rodríguez ◽

Iolanda Spera ◽

Francisca C. Venegas ◽

Maria Favia ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Signaling Networks ◽

Oxygen Species ◽

Cellular Processes ◽

Pathological Conditions ◽

Mitochondrial Ros ◽

Ros Formation ◽

Excessive Accumulation

Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles in processes that are different from pathogen killing, as signal transduction, differentiation, and gene expression. The different outcomes of these events are likely to depend on the specific subcellular site of ROS formation, as well as the duration and extent of ROS production. While excessive accumulation of ROS has long been appreciated for its detrimental effects, there is now a deeper understanding of their roles as signaling molecules. This could explain the failure of the “all or none” pharmacologic approach with global antioxidants to treat several diseases. NADPH oxidase is the first source of ROS that has been identified in macrophages. However, growing evidence highlights mitochondria as a crucial site of ROS formation in these cells, mainly due to electron leakage of the respiratory chain or to enzymes, such as monoamine oxidases. Their role in redox signaling, together with their exact site of formation is only partially elucidated. Hence, it is essential to identify the specific intracellular sources of ROS and how they influence cellular processes in both physiological and pathological conditions to develop therapies targeting oxidative signaling networks. In this review, we will focus on the different sites of ROS formation in macrophages and how they impact on metabolic processes and inflammatory signaling, highlighting the role of mitochondrial as compared to non-mitochondrial ROS sources.

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