Role of H2S / reactive sulfur species and its producing enzyme CBS / CTH in adaptive immunity and oral tolerance

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08287
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Showa Pharmaceutical University
• Principal Investigator: AKAHOSHI Noriyuki 昭和薬科大学, 薬学部, 講師 (70534551)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 活性硫黄分子種 / 硫化水素 / 含硫アミノ酸 / システイン / MPST / CTH

Outline of Final Research Achievements

The reactive sulfur species (RSS) produced in the living body has various physiological functions such as cytoprotective effect. The enzymes that produce RSS are known to be cysteine biosynthesis and metabolizing enzymes such as CBS, CTH, and MPST. Studies using gene-deficient mice have revealed that these enzymes act on both exacerbation and alleviation in immune disorders. In this study, various immune disease animal models were tested on Cth and Mpst-deficient mice, and the role of RSS-producing enzymes in the adaptive immune response was investigated. As a result, It was found that hypothermia was exacerbated during passive systemic anaphylaxis in Mpst-deficient mice, suggesting that Mpst may be involved in temperature-related regulatory functions.

Free Research Field

衛生薬学　生化学

Academic Significance and Societal Importance of the Research Achievements

本件で注目した活性硫黄分子種の産生酵素であるCTHとMPSTの遺伝子欠損者は先天的な代謝異常を持つが、平常時は特に症状は見られないため、発見自体が稀である。しかし遺伝子欠損マウスを用いた研究から、栄養補給の不全やある種の薬剤の使用により肝不全などの生命に関わる急激な病変リスクがある。本研究では、緊急を要するアナフィラキシーショック時において、システイン代謝あるいは活性硫黄分子種の産生経路の破綻した場合のリスクをはじめて示唆した。