Analysis of the role of sulfur amino acids metabolism in renal proximal tubules using mice lacking cysteine-producing enzymes

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790219
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Akita University (2011); Keio University (2010)
• Principal Investigator: AKAHOSHI Noriyuki 秋田大学, 大学院・医学系研究科, 助教 (70534551)
• Project Period (FY): 2010 – 2011
• Keywords: 含硫アミノ酸 / Cystathionine β-synthase (CBS) / Cystathionine γ-lyase (CSEまたはCTH) / 硫化水素 / ホモシスチン尿症 / 妊娠高血圧腎症

Research Abstract

Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are the transsulfuration enzymes that are involved in sulfur amino acids metabolism. CBS-deficient patients show severe clinical symptoms, while CSE-deficient persons are considered to be free of any clinical manifestations. Although both enzymes are primarily expressed in the liver and the kidney of mice, their roles in the kidney remain to be elucidated. In CBS-deficient mice, the urinary excretion of toxic methionine was much lower efficiency, while the cystathionine was efficiently excreted into the urine in CSE-deficient mice. The efficiency of excretion is considered to be related to the difference of symptoms. Pregnancy-induced hypertension and proteinuria was developed in normal-appearing CSE-deficient mice. H2S that has vasorelaxant activity is known to be produced by CBS and CSE, and its distribution was overlapped with both enzymes in kidney.

Research Products

• [Journal Article] Methionine excess in diet induces acute lethal hepatitis in mice lacking cystathionine γ-lyase, an animal model of cystathioninuria (2012)
  • Author(s): Yamada H, Akahoshi N, Kamata S, Hagiya Y, Hishiki T, Nagahata Y, Matsuura T, Takano N, Mori M, Ishizaki Y, Izumi T, Kumagai Y, Kasahara T, Suematsu M, Ishii I
  • Journal Title: Free Radic Biol Med Volume: 52 Pages: 1716-1726
  • Peer Reviewed
• [Journal Article] TOF-SIMS imaging of halide/thiocyanate anions and hydrogen sulfide in mouse kidney sections using silver-deposited plates (2011)
  • Author(s): Akahoshi N, Ishizaki I, Naya M, Maekawa T, Yamazoe S, Horiuchi T, Kajimura M, Ohashi Y, Suematsu M, Ishii I
  • Journal Title: Anal. Bioanal. Chem Volume: 402 Pages: 1859-1864
  • Peer Reviewed
• [Journal Article] Triacylglycerol/phospholipid molecular species profiling of fatty livers and regenerated non-fatty livers in cystathionine beta-synthase-deficient mice, an animal model for homocysteinemia/homocystinuria (2011)
  • Author(s): Ikeda K, Kubo A, Akahoshi N, Yamada H, Miura N, Hishiki T, Nagahata Y, Matsuura T, Suematsu M, Taguchi R, Ishii I
  • Journal Title: Anal. Bioanal. Chem Volume: 400 Pages: 1853-1863
  • Peer Reviewed
• [Journal Article] Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury (2010)
  • Author(s): Ishii I, Akahoshi N, Yamada H, Nakano S, Izumi T, Suematsu M
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 26358-26368
  • Peer Reviewed
• [Presentation] Pregnancy-induced hypertension and proteinuria in hyperhomocysteinemic mice (2010)
  • Author(s): Akahoshi N, Suematsu M, Ishii I
  • Organizer: 日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20101200