Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
In 1970s, marked inhibition of 5-aminolevulinate dehydratase (ALAD) was well known as the specific and sensitive indicator of lead., resulting hypochromic anemia. Replacement of zinc by lead inhibited purified ALAD, which was reactivated by reconstruction of zinc binding to essential SH residues. It was showen that almost 90% of ALAD activity in vivo was determined by molar ratios among ALAD, and lead as well as zinc and GSH in all tissues examined. The result agreed with observations supporting absence of isozyme.Generating trichloroethylene-epoxide also efficiently inhibited ALAD, without any reactivation. Hepatic ALAD inhibition decreased either CYP and heme saturation of tryptophan pyrrolase, showing deficient free heme pool. Furthermore, hepatic 5-aminolevulinate synthase (ALAS), the rate-limiting step, was markedly induced, suggesting a negative feedback. Erythroid ALAS, immunochemically isozyme of hepatic ALAS, showed a positive regulation by heme, a part of which was mediated by Bach-1. These results were in good agreement with a difference between hepatic and erythropoietic porphyria, i.e. presence and absent of acute neuro-onset. Based on studies by others as well as ours, Japanese Government approved hemin as orphan drug for hepatic porphyria, in 2011.In 1990s, past exposure of asbestos and coming increase of mesothelioma became one of the most sever health problems in Japan. One of members in our laboratory (H. W.) succeeded to prevent carcinogenesis by NKT cells in mice, hence we started to develop similar method in human on 2006. Mucosal associated invariant T (MAIT) cells whose characteristics resembles NKT cells were abundant in human. By 2013, human MAIT cells derived from iPS cells (reMAIT) indicated ability to prevent infection of mycobacteria. Successive studies reveal preventive activity of reMAIT cells on cancer in 2022.
