Harnessing Computational Methods for Uncovering Structural Insights into Leishmania donovani 3- MST: Implications for Drug Design and Target Specificity DOI Creative Commons
Ravi Ranjan, Rashmi Kumari, Ashish Kumar

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Abstract 3-Mercaptopyruvate sulfurtransferase (3-MST) is an enzyme that plays integral roles in various biological processes. In the realm of Leishmania, role 3-MST less explored. It a critical player maintaining oxidative homeostasis Leishmania during stress for survival. This highlights potential Ld3-MST as appealing drug target. However, recognising structural disparities becomes essential when protein present host and parasite. study delves into distinctions between Hs3-MST, providing valuable insights with direct implications design. A standout feature elongated 70 amino acid C-terminal mainly contributing to lid-like domain above active site cavity, setting it apart from Hs3-MST. The RMSD analysis shows fluctuation due extended tail, while Rg SASA confirm open solvent-accessible nature Ld3-MST, especially its site, suggesting ability accommodate larger molecules. PC FEL reveals unique internal molecular dynamics particularly site. Docking studies demonstrate Ld3-MST's can effectively molecules, highlighting comprehensive investigation lays foundation developing precise inhibitors promising therapeutic applications.

Language: Английский

Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis—A Comprehensive One-Year Review DOI Creative Commons
Constantin Munteanu, Marius Turnea, Mariana Rotariu

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1737 - 1737

Published: Sept. 7, 2023

Hydrogen sulfide (H2S), traditionally recognized as a toxic gas, has emerged critical regulator in many biological processes, including oxidative stress and cellular homeostasis. This review presents an exhaustive overview of the current understanding H2S its multifaceted role mammalian functioning management. We delve into sources function H2S, mechanisms underlying homeostasis, intricate relationships between these processes. explore evidence from recent experimental clinical studies, unraveling biochemical molecular dictating H2S’s roles modulating responses maintaining The implications therapeutic potential conditions characterized by dysregulation disrupted homeostasis are discussed, highlighting emerging significance health disease. Finally, this underscores challenges, controversies, future directions field, emphasizing need for further research to harness agent diseases associated with homeostatic imbalance. Through review, we aim emphasize pivotal function, encouraging exploration burgeoning area research.

Language: Английский

Citations

34

Chemistry of Hydrogen Sulfide—Pathological and Physiological Functions in Mammalian Cells DOI Creative Commons
Celia María Curieses Andrés, José Manuel Pérez de la Lastra, Celia Andrés

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(23), P. 2684 - 2684

Published: Nov. 22, 2023

Hydrogen sulfide (H

Language: Английский

Citations

25

Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review DOI Creative Commons
R.A. Youness, Danira Ashraf Habashy,

Nour Khater

et al.

Non-Coding RNA, Journal Year: 2024, Volume and Issue: 10(1), P. 7 - 7

Published: Jan. 18, 2024

Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a “Maestro” role in orchestrating several oncological non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although significant amount work has been conducted on nitric oxide (NO) carbon monoxide (CO) inter-relationship field oncology, research about hydrogen sulfide (H2S) remains its infancy. non-coding RNAs (ncRNAs) reported dominating regulation endogenous machinery system H2S pathological contexts. A growing list microRNAs (miRNAs) long (lncRNAs) are leading way upstream regulators for biosynthesis different mammalian cells during development progression human diseases; therefore, targeting can be great benefit. In current review, authors shed light onto biosynthetic pathways by miRNAs lncRNAs various disorders.

Language: Английский

Citations

10

The Role of Hydrogen Sulfide (H2S) in Epigenetic Regulation of Neurodegenerative Diseases: A Systematic Review DOI Open Access

Bombonica Gabriela Dogaru,

Constantin Munteanu

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12555 - 12555

Published: Aug. 8, 2023

This review explores the emerging role of hydrogen sulfide (H

Language: Английский

Citations

21

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer DOI Creative Commons
Alyaa Dawoud, R.A. Youness,

Heba Nafea

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 16, 2024

Abstract Background Hydrogen sulfide (H 2 S) is a significant endogenous mediator that has been implicated in the progression of various forms cancer including breast (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are three principal mammalian enzymes responsible for H S production. Overexpression CBS, CSE 3MST was found to be associated with poor prognosis BC patients. Moreover, linked an immune-suppressive tumor microenvironment BC. Recently it observed cells, response single or dual inhibition synthesizing enzymes, develop escape mechanism by overexpressing alternative sources generation. Thus, aim this work compensatory pan repressing using microRNAs (miRNAs) investigate their impact on oncogenic immunogenic profile cells. Methods female patients ( n = 25) were recruited. In-silico analysis used identify miRNAs targeting CSE, 3MST. MDA-MB-231 cells cultured transfected oligonucleotides. Total RNA extracted Biazol, reverse transcribed quantified qRT-PCR. levels measured AzMc assay. hallmarks assessed trans-well migration, wound healing, MTT, colony forming assays. Results miR-193a miR-548c validated eight different bioinformatics software simultaneously target MiR-193a significantly downregulated tissues compared non-cancerous counterparts. Ectopic expression TNBC resulted marked repression transcript protein levels, decrease reduction cellular viability, migration ability, immune-suppressor proteins GAL3 GAL9, CD155 upregulation immunostimulatory MICA MICB proteins. Conclusion This study sheds light onto as potential pan-repressors enzymes. identifies them novel suppressor immunomodulatory TNBC.

Language: Английский

Citations

6

Hydrogen Sulfide Modulation of Matrix Metalloproteinases and CD147/EMMPRIN: Mechanistic Pathways and Impact on Atherosclerosis Progression DOI Creative Commons
Constantin Munteanu, Anca‐Irina Galaction, Mădălina Poştaru

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1951 - 1951

Published: Aug. 26, 2024

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation potential cardiovascular events. Key players in ECM inflammation are metalloproteinases (MMPs) CD147/EMMPRIN, surface glycoprotein expressed on cells, vascular smooth muscle cells (VSMCs), immune that regulates MMP activity. Hydrogen sulfide (H₂S), gaseous signaling molecule, has emerged as significant modulator of these processes including oxidative stress mitigation, reduction, remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs CD147/EMMPRIN assesses its impact atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, Web Science databases, focusing studies examining modulation contexts. Findings indicate modulates expression activity transcriptional regulation post-translational modifications, S-sulfhydration. By mitigating stress, reduces activation, contributing stability also downregulates via pathways, diminishing responses cellular proliferation plaques. The dual regulatory role inhibiting downregulating CD147 suggests therapeutic agent stabilizing atherosclerotic plaques inflammation. Further research warranted elucidate precise molecular mechanisms explore H₂S-based therapies for clinical application atherosclerosis.

Language: Английский

Citations

5

A structural optimized fluorescent probe for monitoring hydrogen sulfide in cells and zebrafish DOI
Mengya Guo, Yun‐Zhang Li,

X. H. Liu

et al.

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Journal Year: 2023, Volume and Issue: 309, P. 123763 - 123763

Published: Dec. 11, 2023

Language: Английский

Citations

12

Protective Role of Taurine on Rat Offspring Hypertension in the Setting of Maternal Chronic Kidney Disease DOI Creative Commons
You‐Lin Tain, Chih‐Yao Hou,

Guo‐Ping Chang‐Chien

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2059 - 2059

Published: Nov. 29, 2023

Taurine is a natural antioxidant with antihypertensive properties. Maternal chronic kidney disease (CKD) has an impact on renal programming and increases the risk of offspring hypertension in later life. The underlying mechanisms cover oxidative stress, dysregulated hydrogen sulfide (H2S) system, dysbiotic gut microbiota, inappropriate activation renin-angiotensin-aldosterone system (RAAS). We investigated whether perinatal taurine administration enables us to prevent high blood pressure (BP) complicated by maternal CKD. Before mating, CKD was induced through feeding chow containing 0.5% adenine for 3 weeks. administered (3% drinking water) during gestation lactation. Four groups male were used (n = 8/group): controls, CKD, taurine-treated control rats, rats treatment significantly reduced BP born mothers beneficial effects attributed augmented H2S pathway, rebalance aberrant RAAS activation, microbiota alterations. In summary, our results not only deepen knowledge CKD-induced but also afford impetus consider taurine-based intervention as promising preventive approach future clinical translation.

Language: Английский

Citations

11

CSE/H2S Signaling Pathways in Enhancing Muscle Function and Insulin Sensitivity During Exercise DOI Open Access
Miaomiao Xu, Xiaoguang Liu,

Danhong Hu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1741 - 1741

Published: Feb. 18, 2025

Exercise plays a crucial role in maintaining metabolic health, enhancing muscle function, and improving insulin sensitivity, thereby preventing diseases such as type 2 diabetes. Emerging evidence highlights the significance of cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) signaling pathway pivotal regulator molecular physiological adaptations induced by exercise. This review comprehensively examines biosynthesis metabolism H2S, its distribution different tissues, mechanisms which CSE/H2S influences contraction, repair, protein synthesis. Additionally, it explores how modulates pathways, glucose uptake, lipid metabolism, sensitivity. The potential H2S donors exercise supplements is also discussed, highlighting their ability to improve performance health. Current research advancements, including application multi-omics approaches, are reviewed provide deeper understanding complex networks involved. Furthermore, challenges future directions addressed, emphasizing need for further mechanistic studies clinical applications. underscores therapeutic targeting optimize benefits

Language: Английский

Citations

0

The Selective 3-MST Inhibitor I3MT-3 Works as a Potent Caspase-1 Inhibitor DOI Open Access

Kohei Otani,

Ryuto Komatsu,

Takuya Noguchi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2237 - 2237

Published: March 2, 2025

I3MT-3 (HMPSNE) has been identified as a selective inhibitor of the supersulfide-producing enzyme 3-MST. In this study, we found that inhibits inflammatory responses, including secretion pro-inflammatory cytokine interleukin-1β (IL-1β) and cell death pyroptosis, induced by activation inflammasomes composed NLRP1, NLRP3, or AIM2. However, interestingly, knockdown 3-MST did not affect inflammasomes, suggesting inhibitory effect on inflammasome is mediated alternative ways rather than inhibition Interestingly, an in vitro caspase assay revealed directly caspase-1 activation, molecular docking simulations raised possibility pyrimidone ring stabilizes direct interaction with caspase-1. Taken together, our data suggest targeting caspase-1, show potent

Language: Английский

Citations

0