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Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis.
Free Radic Biol Med. 2017 11; 112:423-432.FR

Abstract

Cystathionine γ-lyase (CSE), the last key enzyme of the transsulfuration pathway, is involved in the production of hydrogen sulfide (H2S) and glutathione (GSH), which regulate redox balance and act as important antioxidant molecules. Impairment of the H2S- and GSH-mediated antioxidant system is associated with the progression of chronic kidney disease (CKD), characterized by kidney fibrosis and dysfunction. Here, we evaluated the role of CSE in the progression of kidney fibrosis after unilateral ureteral obstruction (UUO) using mice deficient in the Cse gene. UUO of wild-type mice reduced the expression of H2S-producing enzymes, CSE, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase in the obstructed kidneys, resulting in decreased H2S and GSH levels. Cse gene deletion lowered H2S and GSH levels in the kidneys. Deleting the Cse gene exacerbated the decrease in H2S and GSH levels and increase in superoxide formation and oxidative damage to proteins, lipids, and DNA in the kidneys after UUO, which were accompanied by greater kidney fibrosis, deposition of extracellular matrixes, expression of α-smooth muscle actin, tubular damage, and infiltration of inflammatory cells. Furthermore, Cse gene deletion exacerbated mitochondrial fragmentation and apoptosis of renal tubule cells after UUO. The data provided herein constitute in vivo evidence that Cse deficiency impairs renal the H2S- and GSH-producing activity and exacerbates UUO-induced kidney fibrosis. These data propose a novel therapeutic approach against CKD by regulating CSE and the transsulfuration pathway.

Authors+Show Affiliations

Department of Anatomy, Cardiovascular Research Institute and BK21 Plus, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.Department of Anatomy, Cardiovascular Research Institute and BK21 Plus, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.Department of Molecular Medicine, BK21 Plus, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.Laboratory of Health Chemistry, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.Department of Molecular Medicine, BK21 Plus, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea.Department of Molecular Medicine and MRC, College of Medicine, Keimyung University, 1095 Dalgubeol-daero 250-gil, Dalseogu, Daegu 42601, Republic of Korea.Department of Anatomy, Cardiovascular Research Institute and BK21 Plus, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Junggu, Daegu 41944, Republic of Korea. Electronic address: kmpark@knu.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28842346

Citation

Han, Sang Jun, et al. "Hydrogen Sulfide-producing Cystathionine Γ-lyase Is Critical in the Progression of Kidney Fibrosis." Free Radical Biology & Medicine, vol. 112, 2017, pp. 423-432.
Han SJ, Noh MR, Jung JM, et al. Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis. Free Radic Biol Med. 2017;112:423-432.
Han, S. J., Noh, M. R., Jung, J. M., Ishii, I., Yoo, J., Kim, J. I., & Park, K. M. (2017). Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis. Free Radical Biology & Medicine, 112, 423-432. https://doi.org/10.1016/j.freeradbiomed.2017.08.017
Han SJ, et al. Hydrogen Sulfide-producing Cystathionine Γ-lyase Is Critical in the Progression of Kidney Fibrosis. Free Radic Biol Med. 2017;112:423-432. PubMed PMID: 28842346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis. AU - Han,Sang Jun, AU - Noh,Mi Ra, AU - Jung,Jung-Min, AU - Ishii,Isao, AU - Yoo,Jeongsoo, AU - Kim,Jee In, AU - Park,Kwon Moo, Y1 - 2017/08/24/ PY - 2017/06/08/received PY - 2017/07/29/revised PY - 2017/08/21/accepted PY - 2017/8/27/pubmed PY - 2018/5/31/medline PY - 2017/8/27/entrez KW - Chronic kidney disease KW - Cystathionine γ-lyase KW - Hydrogen sulfide KW - Kidney fibrosis KW - Reactive oxygen species SP - 423 EP - 432 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 112 N2 - Cystathionine γ-lyase (CSE), the last key enzyme of the transsulfuration pathway, is involved in the production of hydrogen sulfide (H2S) and glutathione (GSH), which regulate redox balance and act as important antioxidant molecules. Impairment of the H2S- and GSH-mediated antioxidant system is associated with the progression of chronic kidney disease (CKD), characterized by kidney fibrosis and dysfunction. Here, we evaluated the role of CSE in the progression of kidney fibrosis after unilateral ureteral obstruction (UUO) using mice deficient in the Cse gene. UUO of wild-type mice reduced the expression of H2S-producing enzymes, CSE, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase in the obstructed kidneys, resulting in decreased H2S and GSH levels. Cse gene deletion lowered H2S and GSH levels in the kidneys. Deleting the Cse gene exacerbated the decrease in H2S and GSH levels and increase in superoxide formation and oxidative damage to proteins, lipids, and DNA in the kidneys after UUO, which were accompanied by greater kidney fibrosis, deposition of extracellular matrixes, expression of α-smooth muscle actin, tubular damage, and infiltration of inflammatory cells. Furthermore, Cse gene deletion exacerbated mitochondrial fragmentation and apoptosis of renal tubule cells after UUO. The data provided herein constitute in vivo evidence that Cse deficiency impairs renal the H2S- and GSH-producing activity and exacerbates UUO-induced kidney fibrosis. These data propose a novel therapeutic approach against CKD by regulating CSE and the transsulfuration pathway. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/28842346/Hydrogen_sulfide_producing_cystathionine_γ_lyase_is_critical_in_the_progression_of_kidney_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(17)30733-5 DB - PRIME DP - Unbound Medicine ER -