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Shouzhe Lin, Dameng Lian, Weihua Liu, Aaron Haig, Ian Lobb, Ahmed Hijazi, Hassan Razvi, Jeremy Burton, Matthew Whiteman, Alp Sener
OBJECTIVES: To assess the effects of slow-releasing H2 S donor GYY4137 on post-obstructive renal function and injury following unilateral ureteral obstruction (UUO) by using the UUO and reimplantation (UUO-R) model in rats and to elucidate potential mechanisms by using an in vitro model of epithelial-mesenchymal transition (EMT). METHODS: Male Lewis rats underwent UUO at the left ureterovesical junction. From post-obstructive day (POD) 1-13, rats received daily intraperitoneal (IP) injection of phosphate buffered saline (PBS, 1 mL) or GYY4137 (200 μmol/kg/day in 1 mL PBS, IP)...
March 6, 2018: Nitric Oxide: Biology and Chemistry
Shubhangi Prabhudesai, Chris Koceja, Anindya Dey, Shahram Eisa-Beygi, Noah R Leigh, Resham Bhattacharya, Priyabrata Mukherjee, Ramani Ramchandran
The cystathionine ß-synthase (CBS) is a critical enzyme in the transsulfuration pathway and is responsible for the synthesis of cystathionine from serine and homocysteine. Cystathionine is a precursor to amino acid cysteine. CBS is also responsible for generation of hydrogen sulfide (H2 S) from cysteine. Mutation in CBS enzyme causes homocysteine levels to rise, and gives rise to a condition called hyperhomocysteinuria. To date, numerous mouse knockout models for CBS enzyme has been generated, which show panoply of defects, reflecting the importance of this enzyme in development...
2018: Frontiers in Cell and Developmental Biology
Changnan Wang, Jiankui Du, Shufang Du, Yujian Liu, Dongxia Li, Xiaoyan Zhu, Xin Ni
In a previous study, we showed that endogenous hydrogen sulfide (H2 S) plays a key role in the maintenance of intact adrenal cortex function via the protection of mitochondrial function during endoxemia. We further investigated whether mitochondria-mediated apoptosis is involved in H2 S protection of adrenal function. LPS treatment resulted in mitochondria-mediated apoptosis in the adrenal glands of male mice, and these effects were prevented by the H2 S donor GYY4137. In the model of Y1 cells, the LPS-induced mitochondria-mediated apoptosis and blunt response to ACTH were rescued by GYY4137...
February 24, 2018: Molecular and Cellular Endocrinology
Jin-Zhuo Ning, Wei Li, Fan Cheng, Ting Rao, Wei-Min Yu, Yuan Ruan, Run Yuan, Xiao-Bin Zhang, Yang Du, Cheng-Cheng Xiao
The aim of the present study was to evaluate whether morpholin-4-ium 4 methoxyphenyl (morpholino) phosphonodithioate (GYY4137) exhibits a protective effect on ipsilateral testicular injury in experimentally varicocele (VC)-induced rats. A total of 48 rats were randomly divided into the following 6 groups (n=8 each): Group A (control group); group B (sham group); group C (VC group); group D (VC group administered 5 mg/kg/day GYY4137); group E (VC group administered 10 mg/kg/day GYY4137) and group F (VC group administered 20 mg/kg/day GYY4137)...
January 2018: Experimental and Therapeutic Medicine
Rui Zhuang, Lijia Guo, Juan Du, Songlin Wang, Jun Li, Yi Liu
OBJECTIVE: This study includes exploring (1) the production of endogenous hydrogen sulfide (H2 S) after mucosal wound generation and (2) the role of compensating the change in H2 S level post mucosal wound generation. METHODS AND MATERIALS: A mucosal wound model was established in female C57BL/6J mice. Wound tissues were collected to exam the change in the endogenous H2 S level. To examine the effect of decreased H2 S, GYY4137 was intraperitoneally injected into mice at 50 mg/kg/day before mucosal wounding to compensate for the decreased endogenous H2 S...
January 30, 2018: Oral Diseases
Congkuo Du, Xianjuan Lin, Wenjing Xu, Fengjiao Zheng, Junyan Cai, Jichun Yang, Qinghua Cui, Chaoshu Tang, Jun Cai, Guoheng Xu, Bin Geng
AIMS: Hydrogen sulfide (H2S) has a protective role in the pathogenesis of atherosclerosis by multiple pathways. Sirtuin-1 (SIRT1) is a histone deacetylase, as an essential mediated longevity gene, and has an anti-atherogenic effect by regulating the acetylation of some functional proteins. Whether SIRT1 is involved in protecting H2S in atherosclerosis and its mechanism remains unclear. RESULTS: In ApoE-knockout atherosclerosis mice, treatment with an H2S donor (NaHS or GYY4137) reduced atherosclerotic plaque area, macrophage infiltration, aortic inflammation and plasma lipid level...
January 17, 2018: Antioxidants & Redox Signaling
Natalie A Drucker, Amanda R Jensen, Michael Ferkowicz, Troy A Markel
BACKGROUND: Necrotizing enterocolitis (NEC) continues to be a morbid surgical condition among preterm infants. Novel therapies for this condition are desperately needed. Hydrogen sulfide (H2 S) is an endogenous gasotransmitter that has been found to have beneficial properties. We therefore hypothesized that intraperitoneal injection of various H2 S donors would improve clinical outcomes, increase intestinal perfusion, and reduce intestinal injury in an experimental mouse model of necrotizing enterocolitis...
December 24, 2017: Journal of Pediatric Surgery
Xu Cao, Siping Xiong, Yebo Zhou, Zhi-Yuan Wu, Lei Ding, Yike Zhu, Mark Wood, Matthew Whiteman, Philip K Moore, Jin-Song Bian
AIMS: Cisplatin is a major therapeutic drug for solid tumors, but can cause severe nephrotoxicity. However, the role and therapeutic potential of hydrogen sulfide (H2S), an endogenous gaso-transmitter, in cisplatin-induced nephrotoxicity remains to be defined. RESULTS: Cisplatin led to the impairment of H2S production in vitro and in vivo by downregulating the expression level of cystathionine γ-lyase (CSE), which may contribute to the subsequent renal proximal tubule (RPT) cell death and thereby renal toxicity...
January 9, 2018: Antioxidants & Redox Signaling
Mariela Castelblanco, Jérôme Lugrin, Driss Ehirchiou, Sonia Nasi, Isao Ishii, Alexander So, Fabio Martinon, Nathalie Busso
A variety of stimuli, including monosodium urate (MSU) crystals, activate the NLRP3 inflammasome, and this activation involves several molecular mechanisms including xanthine oxidase (XO) upregulation and mitochondrial dysfunction. Upon oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 becomes active and cleaves the proinflammatory cytokine IL-1β into its active secreted form. Hydrogen sulfide (H2S), a gasotransmitter mainly produced by cystathionine γ-lyase (CSE) in macrophages, could modulate inflammation...
December 26, 2017: Journal of Biological Chemistry
Patrick B Murphy, Aurelia Bihari, Neil G Parry, Ian Ball, Ken Leslie, Kelly Vogt, Abdel-Rahman Lawendy
BACKGROUND: Carbon monoxide (CO)- and hydrogen sulphide-releasing molecules (CORM-3 and GYY4137, respectively) have been shown to be potent antioxidant and antiinflammatory agents at the tissue and systemic level. We hypothesized that both CORM-3 and GYY4137 would reduce the significant organ dysfunction associated with abdominal compartment syndrome (ACS). MATERIAL AND METHODS: Randomized trial was conducted where ACS was maintained for 2 hours in 27 rats using an abdominal plaster cast and intraperitoneal CO2 insufflation at 20 mmHg...
February 2018: Journal of Surgical Research
Meng Lu, Xian Jiang, Liquan Tong, Feng Zhang, Lin Ma, Xuesong Dong, Xueying Sun
Maintaining a certain level of hydrogen sulfide (H2 S) in ischemia-reperfusion (I/R) is essential for limiting injury to the liver. Exogenous H2 S exerts protective effects against this injury, but the mechanisms remain unclear. Liver injury was induced in Wistar rats undergoing hepatic I/R for 30 min, followed by a 3-h reperfusion. Administration of GYY4137 (a slow-releasing H2 S donor) significantly attenuated the severity of liver injury and was reflected by reduced inflammatory cytokine production and cell apoptosis, the levels of which were elevated by I/R, while DL-propargylglycine (PAG, an inhibitor of cystathionine γ-lyase [CSE]) aggravated liver injury...
February 1, 2018: Biological & Pharmaceutical Bulletin
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 H2 S 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 H2 S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active...
2017: Frontiers in Pharmacology
Xiaoou Hou, Yuqing Yuan, Yulan Sheng, Baoshi Yuan, Yali Wang, Jiyue Zheng, Chun-Feng Liu, Xiaohu Zhang, Li-Fang Hu
The neuromodulator hydrogen sulfide (H2 S) 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 H2 S 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
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
Csaba Szabo, Andreas Papapetropoulos
Over the last decade, hydrogen sulfide (H2 S) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, H2 S is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. H2 S 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
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
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
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
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
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
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