title: Expression profile of hydrogen sulfide and its synthases correlates with tumor stage and grade in urothelial cell carcinoma of bladder.
abstract: BACKGROUND
  Hydrogen sulfide (H2S) is a newly discovered gas transmitter. It is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST). Endogenous hydrogen sulfide has never been studied in bladder cancer.
  
  
  OBJECTIVE
  We evaluated H2S production and its synthases expression levels in transitional cell carcinoma (urothelial cell carcinoma of bladder [UCB]) of human bladder tissue and cell lines.
  
  
  METHODS
  Immunostaining was performed in urothelial cell lines and bladder specimens from 94 patients with UCB of different stages/grades. The expression levels/activities of CBS, CSE, and MPST of specimens and cell lines were analyzed by image semiquantity assay, western blot, and a sulfur-sensitive electrode. We tried to find the correlation between hydrogen sulfide and its synthases with tumor stage in UCB. All experiments were repeated at least 3 times.
  
  
  RESULTS
  Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined and cultured cells. The expression levels of CBS, CSE, and MPST were associated with UCB stage/grade. Muscle-invasive bladder cancer samples showed the highest production of H2S (52.6±2.91 nmol/[mg·min]) among all tested samples and EJ cells (transitional cell carcinoma, grade IIIshowed the highest production of H2S among all tested cell lines (53.3±7.02nmol/[mg·min]).
  
  
  CONCLUSIONS
  Protein levels and catalytic activities of CBS, CSE, and MPST increased with the increase of malignant degrees in human bladder tissues and human UCB cell lines. Our findings may promote the application of these novel enzymes to UCB diagnosis or treatment.
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China.
authors: Jun-Wei
authors: JW
authors: Gai
authors: Department of orthopedics, Xiangyang Central Hospital, Xiangyang, P.R. China.
authors: Wei
authors: W
authors: Qin
authors: Hedong Center for Disease Control and Prevention, Tianjin, P.R. China.
authors: Miao
authors: M
authors: Liu
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China.
authors: Hai-Feng
authors: HF
authors: Wang
authors: Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, P.R. China.
authors: Min
authors: M
authors: Zhang
authors: Department of Urology, The People׳s Hospital of Nanpi Country, Nanpi, P.R. China.
authors: Meng
authors: M
authors: Li
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China.
authors: Wen-Hui
authors: WH
authors: Zhou
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China.
authors: Qin-Tong
authors: QT
authors: Ma
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China.
authors: Guang-Ming
authors: GM
authors: Liu
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China.
authors: Wen-Hui
authors: WH
authors: Song
authors: Department of Urology, Peking University First Hospital, The Institute of Urology, Peking University, Beijing, P.R. China.
authors: Jie
authors: J
authors: Jin
authors: Department of Urology, Tianjin First Central Hospital, Tianjin, P.R. China. Electronic address: ghduro@126.com.
authors: Hong-Shun
authors: HS
authors: Ma
mesh_terms: D000368:Aged; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis* / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D013466:Sulfurtransferases / Q000096:biosynthesis* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology
chemical_list: D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: 3-Mercaptopyruvate sulfurtransferase; Cystathionine β-synthase; Cystathionine γ-lyase; Hydrogen sulfide; Urothelial cell carcinoma of bladder