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GYY4137

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https://www.readbyqxmd.com/read/29163155/intracellular-hyper-acidification-potentiated-by-hydrogen-sulfide-mediates-invasive-and-therapy-resistant-cancer-cell-death
#1
Zheng-Wei Lee, Xin-Yi Teo, Zhi J Song, Dawn S Nin, Wisna Novera, Bok A Choo, Brian W Dymock, Philip K Moore, Ruby Y-J Huang, Lih-Wen Deng
Slow and continuous release of H2S by GYY4137 has previously been demonstrated to kill cancer cells by increasing glycolysis and impairing anion exchanger and sodium/proton exchanger activity. This action is specific for cancer cells. The resulting lactate overproduction and defective pH homeostasis bring about intracellular acidification-induced cancer cell death. The present study investigated the potency of H2S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29163149/gyy4137-an-h2s-slow-releasing-donor-prevents-nitrative-stress-and-%C3%AE-synuclein-nitration-in-an-mptp-mouse-model-of-parkinson-s-disease
#2
Xiaoou Hou, Yuqing Yuan, Yulan Sheng, Baoshi Yuan, Yali Wang, Jiyue Zheng, Chun-Feng Liu, Xiaohu Zhang, Li-Fang Hu
The neuromodulator hydrogen sulfide (H2S) was shown to exert neuroprotection in different models of Parkinson's disease (PD) via its anti-inflammatory and anti-apoptotic properties. In this study, we evaluated the effect of an H2S slow-releasing compound GYY4137 (GYY) on a mouse PD model induced by acute injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). GYY was intraperitoneally (i.p.) injected once daily into male C57BL/6J mice 3 days before and 2 weeks after MPTP (14 mg/kg, four times at 2-h intervals, i...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28986598/hydrogen-sulfide-protects-retinal-ganglion-cells-against-glaucomatous-injury-in-vitro-and-in-vivo
#3
Hanhan Liu, Fabian Anders, Solon Thanos, Carolina Mann, Aiwei Liu, Franz H Grus, Norbert Pfeiffer, Verena Prokosch-Willing
Purpose: Hydrogen sulfide (H2S) is recognized as a novel third signaling molecule and gaseous neurotransmitter. Recently, cell protective properties within the central nervous and cardiovascular system have been proposed. Our purpose was to analyze the expression and neuroprotective effects of H2S in experimental models of glaucoma. Methods: Elevated IOP was induced in Sprague-Dawley rats by means of episcleral vein cauterization. After 7 weeks, animals were killed and the retina was analyzed with label-free mass spectrometry...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28978633/international-union-of-basic-and-clinical-pharmacology-cii-pharmacological-modulation-of-h2s-levels-h2s-donors-and-h2s-biosynthesis-inhibitors
#4
REVIEW
Csaba Szabo, Andreas Papapetropoulos
Over the last decade, hydrogen sulfide (H2S) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, H2S is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. H2S levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer)...
October 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28977784/exogenous-h2s-protects-against-diabetic-cardiomyopathy-by-activating-autophagy-via-the-ampk-mtor-pathway
#5
Fan Yang, Linxue Zhang, Zhaopeng Gao, Xiaojiao Sun, Miao Yu, Shiyun Dong, Jichao Wu, Yajun Zhao, Changqing Xu, Weihua Zhang, Fanghao Lu
BACKGROUND/AIM: Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H2S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H2S via autophagy during high glucose treatment. METHODS: This study investigated the content of H2S in the plasma as well as myocardial, ultrastructural changes in mitochondria and autophagosomes...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28977605/hydrogen-sulfide-and-sulfate-prebiotic-stimulates-the-secretion-of-glp-1-and-improves-glycemia-in-male-mice
#6
Jennifer Pichette, Nancy Fynn-Sackey, Jeffrey Gagnon
Recently, the gastrointestinal microbiome, and its metabolites, has emerged as a potential regulator of host metabolism. However, to date little is known on the precise mechanisms of how this regulation occurs. Hydrogen sulfide (H2S) is abundantly produced in the colon by sulfate-reducing bacteria (SRB). H2S is a bioactive gas that plays regulatory roles in many systems, including metabolic hormone regulation. This gas metabolite is produced in close proximity to the glucagonlike peptide-1 (GLP-1)-secreting cells in the gut epithelium...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28883608/gyy4137-a-hydrogen-sulfide-donor-modulates-mir194-dependent-collagen-realignment-in-diabetic-kidney
#7
A M Sashi Papu John, Sourav Kundu, Sathnur Pushpakumar, Maura Fordham, Gregory Weber, Manas Mukhopadhyay, Utpal Sen
The relationship between hydrogen sulfide (H2S), microRNAs (miRs), matrix metalloproteinases (MMPs) and poly-ADP-ribose-polymerase-1 (PARP-1) in diabetic kidney remodeling remains mostly obscured. We aimed at investigating whether alteration of miR-194-dependent MMPs and PARP-1 causes renal fibrosis in diabetes kidney, and whether H2S ameliorates fibrosis. Wild type, diabetic Akita mice as well as mouse glomerular endothelial cells (MGECs) were used as experimental models, and GYY4137 as H2S donor. In diabetic mice, plasma H2S levels were decreased while ROS and expression of its modulator (ROMO1) were increased...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821460/long-term-effects-of-hydrogen-sulfide-on-the-anabolic-catabolic-balance-of-articular-cartilage-in%C3%A2-vitro
#8
Á Vela-Anero, T Hermida-Gómez, L Gato-Calvo, C Vaamonde-García, S Díaz-Prado, R Meijide-Faílde, F J Blanco, E F Burguera
Healthy cartilage maintenance relies on an equilibrium among the anabolic and catabolic processes in chondrocytes. With the onset of osteoarthritis (OA), increased interleukin (IL)-1β levels induce an inhibition of the synthesis of extracellular matrix (ECM) proteins, as well as an increase in proteases. This eventually leads to a predominance of the catabolic phenotype and the progressive loss of articular cartilage. Hydrogen sulfide (H2S) is a small gaseous molecule recognized as the third endogenous gasotransmitter...
August 15, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28753683/parenteral-na2s-a-fast-releasing-h2s-donor-but-not-gyy4137-a-slow-releasing-h2s-donor-lowers-blood-pressure-in-rats
#9
Adrian Drapala, Dominik Koszelewski, Lenka Tomasova, Ryszard Ostaszewski, Marian Grman, Karol Ondrias, Marcin Ufnal
Hydrogen sulfide (H2S) is involved in blood pressure regulation. We evaluated hemodynamic effects of Na2S and morpholin-4-ium (4-methoxyphenyl)(morpholino)phosphinodithioate (GYY4137), H2S donors. GYY4137 is the most widely studied slow-releasing H2S donor, however, its ability to release H2S under physiological conditions is unclear. Hemodynamics were recorded in anaesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or intraperitoneal (IP) administration of either a vehicle (20% dimethyl sulfoxide), GYY4137 or Na2S...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28740467/phosphonothioate-based-hydrogen-sulfide-releasing-reagents-chemistry-and-biological-applications
#10
REVIEW
Jianming Kang, Deshka L Neill, Ming Xian
Hydrogen sulfide (H2S) is a newly recognized gasotransmitter. Studies have demonstrated that the production of endogenous H2S and the exogenous administration of H2S can regulate many physiological and/or pathological processes. Therefore, H2S releasing agents (also known as H2S donors) are important research tools in advancing our understanding of the biology and clinical potential of H2S. Among currently available donors, GYY4137 is probably the most well-known and has been used in many studies in the past 10 years...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28645584/effects-of-intranasal-treatment-with-slow-gyy4137-and-rapid-nahs-donors-of-hydrogen-sulfide-in-lipopolysaccharide-induced-airway-inflammation-in-mice
#11
Yesim Kaya-Yasar, Yasemin Karaman, Turgut Emrah Bozkurt, Sevgen Celik Onder, Inci Sahin-Erdemli
We have investigated the effects of slow (GYY4137) and rapid (NaHS) hydrogen sulfide (H2S) releasing donors in lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS (0.1 mg/ml) in 60 μl PBS was administered by the intranasal (i.n.) route and control group received vehicle, whereas the subgroups of mice were treated with i.n. GYY4137 or NaHS. The tracheal reactivity, inflammatory cell count in bronchoalveolar lavage (BAL) fluid and lung histopathology were evaluated in all groups 48 h after LPS/PBS applications...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28623294/h2s-and-homocysteine-control-a-novel-feedback-regulation-of-cystathionine-beta-synthase-and-cystathionine-gamma-lyase-in-cardiomyocytes
#12
Shyam Sundar Nandi, Paras Kumar Mishra
Hydrogen sulfide (H2S), a cardioprotective gas, is endogenously produced from homocysteine by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) enzymes. However, effect of H2S or homocysteine on CBS and CSE expression, and cross-talk between CBS and CSE are unclear. We hypothesize that homocysteine and H2S regulate CBS and CSE expressions in a dose dependent manner in cardiomyocytes, and CBS deficiency induces cardiac CSE expression. To test the hypothesis, we treated murine atrial HL1 cardiomyocytes with increasing doses of homocysteine or Na2S/GYY4137, a H2S donor, and measured the levels of CBS and CSE...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615705/a-long-term-and-slow-releasing-hydrogen-sulfide-donor-protects-against-myocardial-ischemia-reperfusion-injury
#13
Xiaotian Sun, Wenshuo Wang, Jing Dai, Sheng Jin, Jiechun Huang, Changfa Guo, Chunsheng Wang, Liewen Pang, Yiqing Wang
Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter exerting various physiological effects, especially in the cardiovascular system. Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing H2S donor, DATS-MSN, using in vivo myocardial ischemia/reperfusion (I/R) models and in vitro hypoxia/reoxygenation cardiomyocyte models. Unlike the instant-releasing pattern of sodium hydrosulphide (NaHS), the release of H2S from DATS-MSN was quite slow and continuous both in the cell culture medium and in rat plasma (elevated H2S concentrations during 24 h and 72 h reperfusion)...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615646/hydrogen-sulfide-stimulates-cftr-in-xenopus-oocytes-by-activation-of-the-camp-pka-signalling-axis
#14
Alexander Perniss, Kathrin Preiss, Marcel Nier, Mike Althaus
Hydrogen sulfide (H2S) has been recognized as a signalling molecule which affects the activity of ion channels and transporters in epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator of electrolyte and fluid homeostasis. In this study, we investigated the regulation of CFTR by H2S. Human CFTR was heterologously expressed in Xenopus oocytes and its activity was electrophysiologically measured by microelectrode recordings. The H2S-forming sulphur salt Na2S as well as the slow-releasing H2S-liberating compound GYY4137 increased transmembrane currents of CFTR-expressing oocytes...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613823/inhibition-of-mitochondrial-bioenergetics-by-esterase-triggered-cos-h2s-donors
#15
Andrea K Steiger, Michela Marcatti, Csaba Szabo, Bartosz Szczesny, Michael D Pluth
Hydrogen sulfide (H2S) is an important biological mediator, and synthetic H2S donating molecules provide an important class of investigative tools for H2S research. Here, we report esterase-activated H2S donors that function by first releasing carbonyl sulfide (COS), which is rapidly converted to H2S by the ubiquitous enzyme carbonic anhydrase (CA). We report the synthesis, self-immolative decomposition, and H2S release profiles of the developed scaffolds. In addition, the developed esterase-triggered COS/H2S donors exhibit higher levels of cytotoxicity than equivalent levels of Na2S or the common H2S donors GYY4137 and AP39...
June 30, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28484204/hydrogen-sulfide-improves-cardiomyocyte-function-in-a-cardiac-arrest-model
#16
Nahuel Aquiles Garcia, Javier Moncayo-Arlandi, Alejandro Vazquez, Patricia Genovés, Conrado J Calvo, José Millet, Nuria Martí, Carmen Aguado, Erwin Knecht, Iñigo Valiente-Alandi, José A Montero, Antonio Díez-Juan, Pilar Sepúlveda
BACKGROUND Cardioplegic arrest is a common procedure for many types of cardiac surgery, and different formulations have been proposed to enhance its cardio-protective effect. Hydrogen sulfide is an important signaling molecule that has cardio-protective properties. We therefore studied the cardio-protective effect of hydrogen sulfide in cardiac cell culture and its potential therapeutic use in combination with cardioplegia formulations. MATERIAL AND METHODS We added hydrogen sulfide donor GYY4137 to HL-1 cells to study its protective effect in nutrient starved conditions...
May 9, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28404873/sulfhydration-associated-phosphodiesterase-5a-dimerization-mediates-vasorelaxant-effect-of-hydrogen-sulfide
#17
Yan Sun, Yaqian Huang, Wen Yu, Siyao Chen, Qiuyu Yao, Chunyu Zhang, Dingfang Bu, Chaoshu Tang, Junbao Du, Hongfang Jin
The study was designed to examine if the vasorelaxant effect of hydrogen sulfide was mediated by sulfhydration-associated phosphodiesterase (PDE) 5A dimerization. The thoracic aorta of rat was separated and the vasorelaxant effects were examined with in vitro vascular perfusion experiments. The dimerization and sulfhydration of PDE 5A and soluble guanylatecyclase (sGC) were measured. PDE 5A and protein kinase G (PKG) activities were tested. Intracellular cGMP content was detected by enzyme-linked immunosorbent assay (ELISA)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404377/h2s-induced-s-sulfhydration-of-lactate-dehydrogenase-a-ldha-stimulates-cellular-bioenergetics-in-hct116-colon-cancer-cells
#18
Ashley A Untereiner, Gabor Oláh, Katalin Módis, Mark R Hellmich, Csaba Szabo
Cystathionine-β-synthase (CBS) is upregulated and hydrogen sulfide (H2S) production is increased in colon cancer cells. The functional consequence of this response is stimulation of cellular bioenergetics and tumor growth and proliferation. Lactate dehydrogenase A (LDHA) is also upregulated in various colon cancer cells and has been previously implicated in tumor cell bioenergetics and proliferation. In the present study, we sought to determine the potential interaction between the H2S pathway and LDH activity in the control of bioenergetics and proliferation of colon cancer, using the colon cancer line HCT116...
July 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28386344/gyy4137-stimulates-osteoblastic-cell-proliferation-and-differentiation-via-an-erk1-2-dependent-anti-oxidant-mechanism
#19
Meng Lv, Yang Liu, Ting-Hui Xiao, Wei Jiang, Bo-Wen Lin, Xiao-Ming Zhang, Yi-Miao Lin, Zhong-Shi Xu
OBJECTIVE: Oxidative stress plays a critical role in the development of osteoporosis. Hydrogen sulfide (H2S), produces anti-oxidant effect in various biological systems. The present study found that GYY4137, a slow H2S releasing compound, stimulated both mRNA level and activity of alkaline phosphatase, the marker of osteoblast differentiation. This research aims to explore the mechanism on how GYY4137 stimulates osteoblastic cell proliferation and differentiation via an ERK1/2-dependent anti-oxidant approach...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28300411/h2s-releasing-polymer-micelles-for-studying-selective-cell-toxicity
#20
Jeffrey C Foster, Scott C Radzinski, Xianlin Zou, Carla V Finkielstein, John B Matson
We report the preparation of S-aroylthiooxime (SATO) functionalized amphiphilic block copolymer micelles that release hydrogen sulfide (H2S), a gaseous signaling molecule of relevance to various physiological and pathological conditions. The micelles release H2S in response to cysteine with a half-life of 3.3 h, which is substantially slower than a related small molecule SATO. Exogenous administration of H2S impacts growth and proliferation of cancer cells; however, the limited control over H2S generation from inorganic sulfide sources results in conflicting reports...
April 3, 2017: Molecular Pharmaceutics
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