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I Lobb, J Jiang, D Lian, W Liu, A Haig, M N Saha, R Torregrossa, M E Wood, M Whiteman, A Sener
Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury...
October 15, 2016: American Journal of Transplantation
S A Coavoy-Sánchez, L Rodrigues, S A Teixeira, A G Soares, R Torregrossa, M E Wood, M Whiteman, S K P Costa, M N Muscará
Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved...
October 6, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
J C van den Born, R Mencke, S Conroy, C J Zeebregts, H van Goor, J L Hillebrands
Atherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen sulfide (H2S) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine γ-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, H2S may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability...
October 6, 2016: Scientific Reports
Guoliang Meng, Yujiao Xiao, Yan Ma, Xin Tang, Liping Xie, Jieqiong Liu, Yue Gu, Ying Yu, Chung-Min Park, Ming Xian, Xin Wang, Albert Ferro, Rui Wang, Philip K Moore, Zhiren Zhang, Hong Wang, Yi Han, Yong Ji
BACKGROUND: Hydrogen sulfide (H2S) is a gasotransmitter that regulates multiple cardiovascular functions. Krüppel-like factor 5 (KLF5) exerts diverse functions in the cardiovascular system. Whether and how H2S regulates KLF5 in myocardial hypertrophy is unknown. METHODS AND RESULTS: In our study, hypertrophic myocardial samples in the clinic were collected and underwent histological and molecular biological analysis. Spontaneously hypertensive rats and neonatal rat cardiomyocytes were studied for functional and signaling responses to GYY4137, an H2S-releasing compound...
September 2016: Journal of the American Heart Association
Vítor S Fernandes, Paz Recio, Elvira López-Oliva, María Pilar Martínez, Ana Sofía Ribeiro, María Victoria Barahona, Ana Cristina Martínez, Sara Benedito, Ángel Agis-Torres, Alberto Cabañero, Gemma M Muñoz, Albino García-Sacristán, Luis M Orensanz, Medardo Hernández
Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition...
September 4, 2016: Pulmonary Pharmacology & Therapeutics
Elena Fernandez Burguera, Rosa Meijide-Failde, Francisco J Blanco
Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases. H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues...
August 29, 2016: Current Drug Targets
Zhiqiang Chen, Zhonghe Zhang, Dongdong Zhang, Hao Li, Zhongye Sun
BACKGROUND AND OBJECTIVE: Increasing studies suggest that miRNAs are served as responders and regulators for pathological change in human. miR-485-5p is such a miRNA that has been proved to be affected by spinal cord I/R injury. This study was to investigate the functional involvement and mechanism of miR-485-5p in sulfuretted hydrogen (H2S) protecting neural cell from injury. METHODS: In this study, serum tumor necrosis factor (TNF-α) and miR-485-5p were detected in 20 patients with spinal cord ischemia/reperfusion (I/R) injury and in 20 healthy control...
September 23, 2016: Biochemical and Biophysical Research Communications
Shanwen Chen, Dingfang Bu, Yuanyuan Ma, Jing Zhu, Lie Sun, Shuai Zuo, Ju Ma, Tengyu Li, Zeyang Chen, Youwen Zheng, Xin Wang, Yisheng Pan, Pengyuan Wang, Yucun Liu
Intestinal barrier injury has been reported to play a vital role in the pathogenesis of endotoxemia. This study aimed to investigate the protective effect of GYY4137, a newly synthesized H2S donor, on the intestinal barrier function in the context of endotoxemia both in vitro and in vivo. Caco-2 (a widely used human colon cancer cell line in the study of intestinal epithelial barrier function) monolayers incubated with lipopolysaccharide (LPS) or TNF-α/IFN-γ and a mouse model of endotoxemia were used in this study...
October 15, 2016: Biochemical Pharmacology
Nadiya Druzhyna, Bartosz Szczesny, Gabor Olah, Katalin Módis, Antonia Asimakopoulou, Athanasia Pavlidou, Petra Szoleczky, Domokos Gerö, Kazunori Yanagi, Gabor Törö, Isabel López-García, Vassilios Myrianthopoulos, Emmanuel Mikros, John R Zatarain, Celia Chao, Andreas Papapetropoulos, Mark R Hellmich, Csaba Szabo
Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the 'Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4-methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H2S) production...
August 10, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Hongyu Zhao, Rui Yan, Xiaogang Zhou, Fang Ji, Bing Zhang
Intestinal barrier involves in the pathogeny of inflammatory bowel disease (IBD) and hydrogen sulfide (H2S) has been reported to improve intestinal barrier integrity. Thus, this study investigated the effects of GYY4137, a slow-release H2S donor, on DSS-induced inflammation and intestinal dysfunction. In vitro model, cellular permeability was significantly increased and expression of tight junctions (ZO-1, Cauldin4, and Occludin) was downregulated in Caco-2 cells. GYY4137 treatment markedly attenuated DSS-induced inflammation and barrier dysfunction...
October 2016: International Immunopharmacology
Qutuba G Karwi, Matthew Whiteman, Mark E Wood, Roberta Torregrossa, Gary F Baxter
Exogenous hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion injury but the mechanism of action is unclear. The present study investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial infarction given specifically at reperfusion and the signalling pathway involved. Thiobutabarbital-anesthetised rats were subjected to 30min of left coronary artery occlusion and 2h reperfusion. Infarct size was assessed by tetrazolium staining. In the first study, animals randomly received either no treatment or GYY4137 (26...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Athanasia Chatzianastasiou, Sofia-Iris Bibli, Ioanna Andreadou, Panagiotis Efentakis, Nina Kaludercic, Mark E Wood, Matthew Whiteman, Fabio Di Lisa, Andreas Daiber, Vangelis G Manolopoulos, Csaba Szabó, Andreas Papapetropoulos
Hydrogen sulfide (H2S) is a signaling molecule with protective effects in the cardiovascular system. To harness the therapeutic potential of H2S, a number of donors have been developed. The present study compares the cardioprotective actions of representative H2S donors from different classes and studies their mechanisms of action in myocardial injury in vitro and in vivo. Exposure of cardiomyocytes to H2O2 led to significant cytotoxicity, which was inhibited by sodium sulfide (Na2S), thiovaline (TV), GYY4137 [morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate], and AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol5yl)phenoxy)decyl) triphenylphospho-nium bromide]...
September 2016: Journal of Pharmacology and Experimental Therapeutics
Mi Liu, Zhanjun Jia, Ying Sun, Aihua Zhang, Tianxin Yang
Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were pretreated with GYY4137 for 72 h prior to cisplatin injection. After cisplatin treatment for 72 h, mice developed obvious renal dysfunction and kidney injury as evidenced by elevated blood urea nitrogen (BUN) and histological damage...
2016: Mediators of Inflammation
Teodora Ivanciuc, Elena Sbrana, Maria Ansar, Nikolay Bazhanov, Csaba Szabo, Antonella Casola, Roberto P Garofalo
RATIONALE: Hydrogen sulfide (H2S) is an endogenous gaseous transmitter whose role in the pathophysiology of several lung diseases has been increasingly appreciated. Our recent studies in vitro have shown for the first time that H2S has an important antiviral and anti-inflammatory activity in respiratory syncytial virus (RSV) infection, the leading cause of bronchiolitis and viral pneumonia in children. OBJECTIVES: To evaluate the therapeutic potential of GYY4137, a novel slow-releasing H2S donor, for prevention and treatment of RSV-induced lung disease, as well as to investigate the role of endogenous H2S in a mouse model of RSV infection...
June 17, 2016: American Journal of Respiratory Cell and Molecular Biology
S Lin, F Visram, W Liu, A Haig, J Jiang, A Mok, D Lian, M E Wood, M Whiteman, I Lobb, A Sener
PURPOSE: Chronic obstructive uropathy can cause irreversible kidney injury, atrophy, and inflammation, which can ultimately lead to fibrosis. Epithelial-mesenchymal transition (EMT) is a key trigger of fibrosis and is caused by upregulation of transforming growth factor beta 1 (TGF-β1) and angiotensin II (ANGII). Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cytoprotective properties. The present study aims to elucidate the effects of the slow-releasing H2S donor GYY4137 on chronic ureteral obstruction and evaluate potential mechanisms...
May 10, 2016: Journal of Urology
Leticia A Montoya, Michael D Pluth
Hydrogen sulfide (H2S) is an essential biological signaling molecule in diverse biological regulatory pathways. To provide new chemical tools for H2S imaging, we report here a fluorescent H2S detection platform (HSN2-BG) that is compatible with subcellular localization SNAP-tag fusion protein methodologies and use appropriate fusion protein constructs to demonstrate mitochondrial and lysosomal localization. We also demonstrate the efficacy of this detection platform to image endogenous H2S in Chinese hamster ovary (CHO) cells and use the developed constructs to report on the subcellular H2S distributions provided by common H2S donor molecules AP39, ADT-OH, GYY4137, and diallyltrisulfide (DATS)...
June 7, 2016: Analytical Chemistry
Amira Moustafa, Yoshiaki Habara
The aim of this study was to define the effects of polysulfide on intracellular Ca(2+) concentration ([Ca(2+)]i) and the underlying machinery, especially from the hydrogen sulfide (H2S) and nitric oxide (NO) perspectives, in rat peritoneal mast cells. We found that a polysulfide donor, Na2S4, increased [Ca(2+)]i, which is both extracellular and intracellular Ca(2+) dependent. Intracellular Ca(2+) release induced by Na2S4 was attenuated by the addition of a ryanodine receptor blocker. A slow-releasing H2S donor, GYY4137, dose dependently increased [Ca(2+)]i that was independent from extracellular Ca(2+) influx...
June 1, 2016: American Journal of Physiology. Cell Physiology
J Kubickova, S Hudecova, L Csaderova, A Soltysova, L Lichvarova, L Lencesova, P Babula, O Krizanova
Cellular differentiation is the process, by which a cell changes from one cell type to another, preferentially to the more specialized one. Calcium fluxes play an important role in this action. Differentiated NG108-15 or PC12 cells serve as models for studying neuronal pathways. NG108-15 cell line is a reliable model of cholinergic neuronal cells. These cells differentiate to a neuronal phenotype due to the dibutyryl cAMP (dbcAMP) treatment. We have shown that a slow sulfide donor - GYY4137 - can also act as a differentiating factor in NG108-15 cell line...
June 14, 2016: Neuroscience
Joseph Candela, Gopal V Velmurugan, Carl White
Structural remodeling of the microvasculature occurs during obesity. Based on observations that impaired H2S signaling is associated with cardiovascular pathologies, the current study was designed to test the hypothesis that altered H2S homeostasis is involved in driving the remodeling process in a diet-induced mouse model of obesity. The structural and passive mechanical properties of mesenteric resistance arterioles isolated from 30-wk-old lean and obese mice were assessed using pressure myography, and vessel H2S levels were quantified using the H2S indicator sulfidefluor 7-AM...
May 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Lubomira Lencesova, Miroslav Vlcek, Olga Krizanova, Sona Hudecova
Hypoxia - a state of lower oxygen demand-is responsible for a higher aggressiveness of tumors and therefore a worse prognosis. During hypoxia, several metabolic pathways are re-organized, e.g., energetic metabolism, modulation of pH, and calcium transport. Calcium is an important second messenger that regulates variety of processes in the cell. Thus, aim of this work was to compare H2S modulation of the intracellular calcium transport systems in hypoxia and in cells grown in standard culture conditions. For all experiments, we used ovarian cancer cell line (A2780)...
March 2016: Molecular and Cellular Biochemistry
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