The sirtuin family in health and disease

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 29, 2022

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, involved numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles members SIRT family health disease conditions. Notably, this protein plays a variety important cellular biology such as inflammation, metabolism, oxidative stress, apoptosis, etc., thus, it is considered potential therapeutic target for different kinds pathologies including cancer, cardiovascular disease, respiratory other Moreover, identification modulators exploring functions these prompted increased efforts discover new small molecules, which can modify activity. Furthermore, several randomized controlled trials indicated that interventions might affect expression human samples, supplementation diverse impact on physiological function participants. In review, we introduce history structure family, discuss molecular mechanisms elaborate regulatory SIRTs summarize inhibitors activators, review related clinical studies.

Язык: Английский

---

Oxidative Stress and Hypertension

Circulation Research, Год журнала: 2021, Номер 128(7), С. 993 - 1020

Опубликована: Апрель 1, 2021

A link between oxidative stress and hypertension has been firmly established in multiple animal models of but remains elusive humans. While initial studies focused on inactivation nitric oxide by superoxide, our understanding relevant reactive oxygen species (superoxide, hydrogen peroxide, peroxynitrite) how they modify complex signaling pathways to promote expanded significantly. In this review, we summarize recent advances delineating the primary secondary sources (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial synthase, endoplasmic reticulum, mitochondria), posttranslational modifications induce protein targets important for redox signaling, their interplay with endogenous antioxidant systems, role inflammasome activation reticular development hypertension. We highlight different organ systems contributes hypertension, describe new that have clarified importance specific proteins, discuss clinical shed light these processes are altered human Finally, focus promise proteomics biology help us fully understand relationship ROS potential designing evaluating novel antihypertensive therapies.

Язык: Английский

---

Mechanisms and consequences of endothelial cell senescence

Nature Reviews Cardiology, Год журнала: 2022, Номер 20(1), С. 38 - 51

Опубликована: Июль 19, 2022

Язык: Английский

---

NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration

Cell Proliferation, Год журнала: 2021, Номер 54(7)

Опубликована: Май 24, 2021

Intervertebral disc degeneration (IDD) is a common clinical degenerative disease of the spine. A series factors, such as inflammation, oxidative stress and mechanical stress, promote degradation extracellular matrix (ECM) intervertebral discs (IVD), leading to dysfunction structural destruction IVD. Nuclear factor-κB (NF-κB) transcription factor has long been regarded pathogenic IDD. Therefore, NF-κB may be an ideal therapeutic target for As multifunctional functional with roles in variety biological processes, comprehensive understanding function regulatory mechanism IDD pathology will useful development targeted strategies IDD, which can prevent progression reduce potential risks. This review discusses role signalling pathway nucleus pulposus (NP) process understand pathological NP further provide targets that interfere therapy.

Язык: Английский

---

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients, Год журнала: 2021, Номер 13(2), С. 690 - 690

Опубликована: Фев. 21, 2021

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest GM can influence health host, several factors modify composition, such as diet, drug intake, lifestyle, geographical locations. Gut dysbiosis affect brain immune homeostasis through microbiota-gut-brain axis play key role pathogenesis neurodegenerative diseases, including dementia Alzheimer's disease (AD). relationship between AD is still elusive, but emerging evidence suggests it enhance secretion lipopolysaccharides amyloids may disturb intestinal permeability blood-brain barrier. In addition, promote hallmarks AD, oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, ultimately causation neural death. Poor dietary habits aging, along with inflammatory responses due to dysbiosis, contribute AD. Thus, modulation probiotics, or fecal transplantation could represent potential therapeutics this review, we discuss therapeutic strategies modulate

Язык: Английский

---

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Язык: Английский

---

Mitigation of honokiol on fluoride-induced mitochondrial oxidative stress, mitochondrial dysfunction, and cognitive deficits through activating AMPK/PGC-1α/Sirt3

Journal of Hazardous Materials, Год журнала: 2022, Номер 437, С. 129381 - 129381

Опубликована: Июнь 16, 2022

Язык: Английский

---

Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Окт. 4, 2022

Abstract Background Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles the maintenance of body metabolism, insulin resistance like. However, protective effect omentin1 myocardial ischemia (MI)-induced heart failure (HF) its specific mechanism remains unclear to be elucidated. Methods The model MI-induced HF mice oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression constructed by fat-specific adeno-associated virus (AAV) vector system. Results We demonstrated that circulating level diminished patients compared healthy subjects. Furthermore, ameliorated cardiac function, hypertrophy, infarct size pathological features, also enhanced SIRT3/FOXO3a signaling mice. Additionally, administration AAV-omentin1 increased mitochondrial fusion decreased fission mice, as evidenced up-regulated expression Mfn2 OPA1, downregulation p-Drp1(Ser616). Then, it promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment recombinant strengthened OGD-injured cardiomyocyte viability, restrained LDH release, accumulation SIRT3 nucleus transduction FOXO3a. Besides, unbalanced fusion-fission dynamics activated mitophagy, thereby, improving damaged mitochondria morphology controlling quality cardiomyocytes. Interestingly, played an important role improvement effects on Conclusion Omentin1 improves injury maintaining dynamical homeostasis activating mitophagy via upregulation signaling. This study provides evidence for further application cardiovascular diseases from perspective tissue.

Язык: Английский

---

Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: focus on mitochondrial dysfunction

Angiogenesis, Год журнала: 2024, Номер 27(4), С. 623 - 639

Опубликована: Июль 26, 2024

Abstract As a vital component of blood vessels, endothelial cells play key role in maintaining overall physiological function by residing between circulating and semi-solid tissue. Various stress stimuli can induce injury, leading to the onset corresponding diseases body. In recent years, importance mitochondria vascular injury has become increasingly apparent. Mitochondria, as primary site cellular aerobic respiration organelle for “energy information transfer,” detect cell damage integrating receiving various external signals. The generation reactive oxygen species (ROS) mitochondrial dysfunction often determine evolution towards necrosis or apoptosis. Therefore, are closely associated with function, helping progression clinical diseases. This article comprehensively reviews interconnection pathogenesis mitochondrial-induced cardiovascular diseases, renal pulmonary-related cerebrovascular microvascular diabetes. Corresponding therapeutic approaches also provided. Additionally, strategies using drugs treat injury-based discussed, aiming offer new insights treatment options diagnosis related injuries.

Язык: Английский

---

2-APQC, a small-molecule activator of Sirtuin-3 (SIRT3), alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 15, 2024

Abstract Sirtuin 3 (SIRT3) is well known as a conserved nicotinamide adenine dinucleotide + (NAD )-dependent deacetylase located in the mitochondria that may regulate oxidative stress, catabolism and ATP production. Accumulating evidence has recently revealed SIRT3 plays its critical roles cardiac fibrosis, myocardial fibrosis even heart failure (HF), through deacetylation modifications. Accordingly, discovery of activators elucidating their underlying mechanisms HF should be urgently needed. Herein, we identified new small-molecule activator (named 2-APQC) by structure-based drug designing strategy. 2-APQC was shown to alleviate isoproterenol (ISO)-induced hypertrophy vitro vivo rat models. Importantly, knockout mice, could not relieve HF, suggesting dependent on for protective role. Mechanically, found inhibit mammalian target rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K), c-jun N-terminal (JNK) transforming growth factor-β (TGF-β)/ small mother against decapentaplegic (Smad3) pathways improve ISO-induced fibrosis. Based upon RNA-seq analyses, demonstrated SIRT3-pyrroline-5-carboxylate reductase 1 (PYCR1) axis closely assoiated with HF. By activating PYCR1, enhance mitochondrial proline metabolism, inhibited reactive oxygen species (ROS)-p38 mitogen activated (p38MAPK) pathway thereby protecting mitochondrialoxidative damage. Moreover, activation facilitate AMP-activated (AMPK)-Parkin necrosis. Together, our results demonstrate targeted alleviates regulating homeostasis, which provide clue exploiting promising candidate future therapeutics.

Язык: Английский

---