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Cystathionine gamma lyase

Claudia Soler-Alfonso, Nishita Pillai, Erin Cooney, Krupa R Mysore, Suzanne Boyer, Fernando Scaglia
Early recognition of rare mitochondrial respiratory chain defects has become readily available with the routine use of whole exome sequencing. Patients with oxidative phosphorylation defects present with a heterogenous phenotype, often rapidly progressive, and lethal. Clinicians aim for prompt identification of the specific molecular defect to provide timely management, decrease morbidity, and potentially improve survival rates. More recently, bi-allelic pathogenic variants in the TRMU gene responsible for encoding the mitochondrial tRNA-specific 2-thiouridylase were found in a syndrome characterized by infantile hepatopathy due to a mitochondrial translation defect (OMIM# 613070)...
June 2019: Molecular Genetics and Metabolism Reports
Alireza Badiei, Raghavi Sudharsan, Evelyn Santana, Joshua L Dunaief, Gustavo D Aguirre
Chronic exposure of the retina to light and high concentrations of polyunsaturated fatty acid in photoreceptor cells make this tissue susceptible to oxidative damage. As retinal degenerative diseases are associated with photoreceptor degeneration, the antioxidant activity of both hydrogen sulfide (H2 S) and glutathione (GSH) may play an important role in ameliorating disease progression. H2 S production is driven by cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS), the key enzymes that also drive transsulfuration pathway (TSP) necessary for GSH production...
January 14, 2019: Experimental Eye Research
Fiona Augsburger, Csaba Szabo
Hydrogen sulfide (H2 S), produced by various endogenous enzyme systems, serves various biological regulatory roles in mammalian cells in health and disease. Over recent years, a new concept emerged in the field of H2 S biology, showing that various cancer cells upregulate their endogenous H2 S production, and utilize this mediator in autocrine and paracrine manner to stimulate proliferation, bioenergetics and tumor angiogenesis. Initial work identified cystathionine-beta-synthase (CBS) in many tumor cells as the key source of H2 S...
November 27, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Eric Stokes, Tian Shuang, Yanjie Zhang, Yanxi Pei, Ming Fu, Baoqing Guo, Amadeo Parissenti, Lingyun Wu, Rui Wang, Guangdong Yang
AIMS: Hydrogen sulfide (H2 S), an important gasotransmitter, is involved in a variety of cellular functions and pathophysiologic processes. Drug resistance due to alterations in drug trafficking and metabolism severely limits the effectiveness of cancer therapy. This study examined the role of H2 S in drug resistance in liver cancer cells. MATERIALS AND METHODS: Human primary hepatocellular carcinoma cell line (HepG2) and doxorubicin (Dox)-resistant cells were used in this study...
October 18, 2018: Life Sciences
Rebecca M Dyson, Hannah K Palliser, Nicole Wilding, Megan A Kelly, Grazyna Chwatko, Rafal Glowacki, Mary J Berry, Xin Ni, Ian M R Wright
OBJECTIVE: H2 S may explain the dysregulation of microvascular tone associated with poor outcome following preterm birth. In adult vasculature, H2 S is predominantly produced by CSE. We hypothesized that vascular CSE activity contributes to microvascular tone regulation during circulatory transition. METHODS: Preterm (GA62) and full-term (GA69) guinea pig fetuses and neonates were studied. Microvascular blood flow was assessed by laser Doppler flowmetry. Thiosulfate, primary urinary metabolite of H2 S, was determined by high-performance liquid chromatography...
October 1, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Yaacov Micha Brog, Sonia Osorio, Yoav Yichie, Saleh Alseekh, Elad Bensal, Kochevenko Andriy, Dani Zamir, Alisdair R Fernie
We present a complementary resource for trait fine-mapping in tomato to those based on the intraspecific cross between cultivated tomato and the wild tomato species Solanum pennellii which have been extensively used for quantitative genetics in tomato over the last twenty years. The current population of backcross inbred lines (BILs) is composed of 107 lines derived after three backcrosses of progeny of the of the wild species S. neorickii (LA2133) and cultivated tomato (cultivar TA209) and is freely available to the scientific community...
September 19, 2018: Plant Journal: for Cell and Molecular Biology
Mélanie Racine, Ming Fu, Tian Shuang, Yanjie Zhang, Yanxi Pei, Lingyun Wu, Rui Wang, Guangdong Yang
Nickel as a heavy metal is known to bring threat to human health, and nickel exposure is associated with changes in fibroblast activation which may contribute to its fibrotic properties. H2 S has recently emerged as an important gasotransmitter involved in numerous cellular signal transduction and pathophysiological responses. Interaction of nickel and H2 S on fibroblast cell activation has not been studied so far. Here, we showed that a lower dose of nickel (200 μM) induced the activation of human fibroblast cells, as evidenced by increased cell growth, migration and higher expressions of α-smooth muscle actin (αSMA) and fibronectin, while high dose of nickel (1 mM) inhibited cell viability...
October 1, 2018: Toxicology and Applied Pharmacology
N Voloshchuk, A Melnik, O Danchenko, V Nechiporuk, N Kosechenko
In studies on 94 male Wistar rats changes in the hydrogen sulfide content (H2S) and cystathionine γ-lyase (CSE) in the liver and skeletal muscles in hypercholesterolemia under simvastatin treatment were assessed, as well as the effect of propargylglycine (PAG) on hepato- and myotoxicity of simvastatin. It was determined, that simvastatin inhibited the CSE-mediated synthesis of H2S in the main target organs. This negatively affected their biochemical and functional status. The use of PAG significantly suppressed the H2S deficiency induced by simvastatin, and also was accompanied by a significant increase in the activity of cytolysis markers in the serum, which significantly and negatively correlated with the activity of CSE and H2S in organs...
June 2018: Georgian Medical News
Shenzheng Mo, Yongmei Hua
Hydrogen sulfide (H2 S), a gaseous signaling molecule produced by cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), influences bone remodeling in many ways. Osteoclasts play an important role in bone remodeling during tooth movement induced by mechanical loading, which increases the rate of tooth movement. Recently, we found that osteoclasts could produce H2 S. However, whether H2 S modulates bone remodeling by affecting osteoclasts remains unclear. In this study, we found that CSE-H2 S was a dominant H2 S generating system in osteoclasts, while CBS did not generate H2 S...
June 22, 2018: Biochemical and Biophysical Research Communications
Fei Tong, Rongkui Chai, Haiying Jiang, Bo Dong
Background: The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2 S). Methods: Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks...
2018: International Journal of Nanomedicine
Needa A Virani, Elangovan Thavathiru, Patrick McKernan, Kathleen Moore, Doris M Benbrook, Roger G Harrison
Approximately 75% of ovarian cancer is diagnosed once metastasis to the peritoneal cavity has occurred. A large proportion of patients eventually develop platinum-resistive tumors, which are considered terminal. In order to provide an alternative a novel fusion protein, mCTH-ANXA5, has been developed for the treatment of recurrent, metastatic ovarian cancer. The fusion protein combines annexin V (ANXA5), an ovarian tumor and tumor vasculature targeting protein, with mutated cystathionine gamma-lyase (mCTH), an enzyme that converts selenomethionine (SeMet) into toxic methylselenol, which generates reactive oxygen species and eventual tumor cell death...
July 1, 2018: Cancer Letters
Bruna M Santos, Emanuela G Garattini, Luiz G S Branco, Christie R A Leite-Panissi, Glauce C Nascimento
Hydrogen sulfide (H2 S) is an endogenous neuromodulator produced mainly by the enzyme cystathionine gamma-lyase (CSE) in peripheral tissues. A pronociceptive role of endogenously produced H2 S has been previously reported by our group in a model of orofacial inflammatory pain. Using the established persistent orofacial pain rat model induced by complete Freund's adjuvant (CFA) injection into temporomandibular joint (TMJ), we have now investigated the putative role of endogenous H2 S modulating hypernociceptive responses...
May 1, 2018: Physiology & Behavior
Saurabh Rajpal, Pavan Katikaneni, Matthew Deshotels, Sibile Pardue, John Glawe, Xinggui Shen, Nuri Akkus, Kalgi Modi, Ruchi Bhandari, Paari Dominic, Pratap Reddy, Gopi K Kolluru, Christopher G Kevil
Hydrogen sulfide (H2 S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adaptation, and mitochondrial respiration. However, bioavailable levels of H2 S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H2 S in patients with and without cardiovascular disease (CVD)...
May 2018: Redox Biology
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
Elisabetta Lambertini, Letizia Penolazzi, Marco Angelozzi, Francesco Grassi, Laura Gambari, Gina Lisignoli, Pasquale De Bonis, Michele Cavallo, Roberta Piva
Hydrogen sulfide (H2 S), generated in the osteoblasts predominantly via cystathionine-γ-lyase (CSE), is bone protective. Previous studies suggested that the onset of bone loss due to estrogen deficiency is associated to decreased levels of H2 S and blunted gene expression of CSE. However, there are still a lot of unknowns on how H2 S levels influence bone cells function. The present study aims to explore the mechanisms by which estrogen may regulate CSE expression, in particular the role of estrogen receptor alpha (ERα) in human osteoblasts (hOBs)...
November 24, 2017: Oncotarget
Tian Shuang, Ming Fu, Guangdong Yang, Lingyun Wu, Rui Wang
Hydrogen sulfide (H2 S) is mostly produced by cystathionine-gamma-lyase (CSE) in vascular system and it inhibits the proliferation of vascular smooth muscle cells (SMCs). Insulin-like growth factor-1 (IGF-1), via its receptor (IGF-1R), exerts multiple physiological and pathophysiological effects on the vasculature, including stimulating SMC proliferation and migration, and inhibiting SMC apoptosis. Since H2 S and IGF-1/IGF-1R have opposite effects on SMC proliferation, it becomes imperative to better understand the interaction of these two signaling mechanisms on SMC proliferation...
March 2018: Biochemical Pharmacology
Guangdong Yang, Youngjun Ju, Ming Fu, Yanjie Zhang, Yanxi Pei, Mélanie Racine, Simran Baath, Thomas J S Merritt, Rui Wang, Lingyun Wu
Hydrogen sulfide (H2 S) has been recognized as an important gasotransmitter analogous to nitric oxide and carbon monoxide. Cystathionine gamma-lyase (CSE)-derived H2 S is implicated in the regulation of insulin resistance and glucose metabolism, but the involvement of CSE/H2 S system in energy homeostasis and fat mass has not been extensively explored. In this study, a potential functional role of the CSE/H2 S system in in vitro adipocyte differentiation and in vivo adipogenesis and the underlying mechanism was investigated...
February 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
David L Kolin, Daniela M Dinulescu, Christopher P Crum
A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinomas suggest that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer...
February 2018: Journal of Pathology
Caitlyn Bourque, Yanjie Zhang, Ming Fu, Mélanie Racine, Adam Greasley, Yanxi Pei, Lingyun Wu, Rui Wang, Guangdong Yang
Hydrogen sulfide (H2 S) is a novel gasotransmitter and acts as a multifunctional regulator in various cellular functions. Past studies have demonstrated a significant role of H2 S and its generating enzyme cystathionine gamma-lyase (CSE) in the cardiovascular system. Lipopolysaccharide (LPS), a major pathogenic factor, is known to initiate the inflammatory immune response. The cross talk between LPS-induced inflammation and the CSE/H2 S system in vascular cells has not yet been elucidated in detail. Here we showed that LPS decreased CSE mRNA and protein expression in human endothelial cells and blocked H2 S production in mouse aorta tissues...
January 1, 2018: Toxicology and Applied Pharmacology
Sanhitha Nandi, Sriram Ravindran, Gino A Kurian
Cardio-protective effect of hydrogen sulfide (H2 S) against myocardial ischemia reperfusion injury (I/R) via preservation of mitochondria is well documented. But the distinct role of exogenous and endogenous H2 S in cardio-protection and its dependency on functional cardiac mitochondria is not understood. The present study was designed to investigate the role of exogenous H2 S preconditioning on cardiac mitochondrial subpopulation namely interfibrillar (IFM) and subsarcolemmal (SSM), in attenuating I/R injury in an isolated rat heart model in the absence of endogenous H2 S production...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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