Cystathionine β-synthase-derived hydrogen sulfide regulates lipopolysaccharide-induced apoptosis of the BRL rat hepatic cell line in vitro

Yan,Jun; Teng,Feixiang; Chen,Weiwei; Ji,Yinglei; Gu,Zhenyong

doi:10.3892/etm.2012.672

Cystathionine β-synthase-derived hydrogen sulfide regulates lipopolysaccharide-induced apoptosis of the BRL rat hepatic cell line in vitro

Authors:
- Jun Yan
- Feixiang Teng
- Weiwei Chen
- Yinglei Ji
- Zhenyong Gu
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Affiliations: Department of Forensic Medicine, Soochow University, Jiangsu 215123, P.R. China, Department of Physiology, Yancheng Institute of Health Science, Jiangsu 224000, P.R. China, Department of Anorectal Surgery, Yancheng Third People's Hospital, Jiangsu 224001, P.R. China
Published online on: August 16, 2012 https://doi.org/10.3892/etm.2012.672
Pages: 832-838

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Abstract

Hydrogen sulfide (H2S), is a member of the novel family of endogenous gaseous transmitters, termed “gasotransmitters exhibiting diverse physiological activities, and is generated in mammalian tissues mainly by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) in conjunction with cysteine (aspartate) aminotranferase (CAT). The distributions of these enzymes are species- and tissue-specific. The liver, as the main organ that generates H2S in vivo, functions in biotransformation and metabolism. However, the liver is vulnerable to damage from internal and external factors, including inflammatory mediators, drugs and poisons. The present study evaluated the endogenous CBS-H2S synthesis regulating lipopolysaccharide (LPS)-induced apoptosis of hepatic cells. The rat hepatic cell line, BRL, was incubated with LPS for various time periods to establish a cell-damage model. Incubation with LPS resulted in a significant increase in CBS expression and H2S production. It also stimulated apoptosis and decreased the mitochondrial membrane potential. Pretreatment with the CBS inhibitor aminooxyacetic acid (AOAA) or CBS small interfering RNA (siRNA) decreased LPS-enhanced H2S production. Notably, apoptosis increased for a short period and then decreased gradually, while the mitochondrial membrane potential demonstrated the opposite trend. These results showed that endogenous CBS-H2S synthesis demonstrated early anti-apoptotic activity and subsequent pro-apoptotic activity in LPS-induced apoptosis. These results suggest a new approach for developing novel drugs for this condition.

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1	Stipanuk MH and Beck PW: Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. Biochem J. 206:267–277. 1982.PubMed/NCBI
2	Swaroop M, Bradley K, Ohura T, Tahara T, Roper MD, Rosenberg LE and Kraus JP: Rat cystathionine-β-synthase. Gene organization and alternative splicing. J Biol Chem. 267:11455–11461. 1992.
3	Shibuya N, Tanaka M, Yoshida M, Ogasawara Y, Togawa T, Ishii K and Kimura H: 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid Redox Signal. 11:703–714. 2009. View Article : Google Scholar : PubMed/NCBI
4	Zhao W, Ndisang JF and Wang R: Modulation of endogenous production of H₂S in rat tissues. Can J Physiol Pharmacol. 81:848–853. 2003. View Article : Google Scholar : PubMed/NCBI
5	Wang R: Two’s company, three’s a crowd: can H₂S be the third endogenous gaseous transmitter? FASEB J. 16:1792–1798. 2002.
6	Moore PK, Bhatia M and Moochhala S: Hydrogen sulfide: from the smell of the past to the mediator of the future? Trends Pharmacol Sci. 24:609–611. 2003. View Article : Google Scholar : PubMed/NCBI
7	Kimura Y, Dargusch R, Schubert D and Kimura H: Hydrogen sulfide protects HT22 neuronal cells from oxidative stress. Antioxid Redox Signal. 8:661–670. 2006. View Article : Google Scholar : PubMed/NCBI
8	Yang GD, Yang W, Wu LY and Wang R: H₂S, endoplasmic reticulum stress, and apoptosis of insulin-secreting beta cells. J Biol Chem. 282:16567–16576. 2007.
9	Li L, Bhatia M and Moore PK: Hydrogen sulphide - a novel mediator of inflammation? Curr Opin Pharmacol. 6:125–129. 2006. View Article : Google Scholar : PubMed/NCBI
10	Gardiner SM, Kemp PA, March JE and Bennett T: Regional haemodynamic responses to infusion of lipopolysaccharide in conscious rat: effects of pre- or post-treatment with glibenclamide. Br J Pharmacol. 128:1772–1778. 1999. View Article : Google Scholar : PubMed/NCBI
11	Shi W, Cui N, Wu Z, Yang Y, Zhang S, Gai HY, Zhu DL and Jiang C: Lipopolysaccharides up-regulate Kir6.1/SUR2B channel expression and enhance vascular KATP channel activity via NF-κB-dependent signaling. J Biol Chem. 285:3021–3029. 2010.PubMed/NCBI
12	Zhao W, Zhang J, Lu Y and Wang R: The vasorelaxant effect of H₂S as a novel endogenous gaseous KATP channel opener. EMBO J. 20:6008–6016. 2001.PubMed/NCBI
13	Szabo G, Mandrekar P and Dolganiuc A: Innate immune response and hepatic inflammation. Semin Liver Dis. 27:339–350. 2007. View Article : Google Scholar : PubMed/NCBI
14	Szabo G, Romics L Jr and Frendl G: Liver in sepsis and systemic inflammatory response syndrome. Clin Liver Dis. 6:1045–1066. 2002. View Article : Google Scholar : PubMed/NCBI
15	Jha S, Calvert JW, Duranski MR, Ramachandran A and Lefer DJ: Hydrogen sulfide attenuates hepatic ischemia-reperfusion injury: role of antioxidant and antiapoptotic signaling. Am J Physiol Heart Circ Physiol. 295:H801–H806. 2008. View Article : Google Scholar : PubMed/NCBI
16	Yang G, Sun X and Wang R: Hydrogen sulfide-induced apoptosis of human aorta smooth muscle cells via the activation of mitogen-activated protein kinases and caspase-3. FASEB J. 18:1782–1784. 2004.PubMed/NCBI
17	Wang R: The gasotransmitter role of hydrogen sulfide. Antioxid Redox Signal. 5:493–501. 2003. View Article : Google Scholar : PubMed/NCBI
18	Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anuar FB, Whiteman M, Salto-Tellez M and Moore PK: Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J. 19:1196–1198. 2005.PubMed/NCBI
19	Hui Y, Du J, Tang C, Bin G and Jiang H: Changes in arterial hydrogen sulfide (H2S) content during septic shock and endotoxin shock in rats. J Infect. 47:155–160. 2003. View Article : Google Scholar : PubMed/NCBI
20	Zhang H, Zhi L, Moore PK and Bhatia M: Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol. 290:1193–1201. 2006. View Article : Google Scholar : PubMed/NCBI
21	Collin M, Anuar FB, Murch O, Bhatia M, Moore PK and Thiemermann C: Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmacol. 146:498–505. 2005. View Article : Google Scholar : PubMed/NCBI
22	Li L, Salto-Tellez M, Tan CH, Whiteman M and Moore PK: GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat. Free Radic Biol Med. 47:103–113. 2009. View Article : Google Scholar : PubMed/NCBI
23	Awata S, Nakayama K, Suzuki I and Kodama H: Effect of cysteine on the inactivation of cystathionine gamma lyase by DL-propargylglycine. Acta Med Okayama. 43:329–335. 1989.PubMed/NCBI
24	Dulak NC and Shing YW: Large scale purification and further characterization of a rat liver cell conditioned medium multiplication stimulating activity. J Cell Physiol. 90:127–137. 1977. View Article : Google Scholar