title: Antioxidant enzyme, 3-mercaptopyruvate sulfurtransferase-knockout mice exhibit increased anxiety-like behaviors: a model for human mercaptolactate-cysteine disulfiduria.
abstract: Human mercaptolactate-cysteine disulfiduria (MCDU) was first recognized and reported in 1968. Most cases of MCDU are associated with mental retardation, while the pathogenesis remains unknown. To investigate it, we generated homozygous 3-mercaptopyruvate sulfurtransferase (MST: EC 2.8.1.2) knockout (KO) mice using C57BL/6 embryonic stem cells as an animal model. The MST-KO mice showed significantly increased anxiety-like behaviors with an increase in serotonin level in the prefrontal cortex (PFC), but not with abnormal morphological changes in the brain. MCDU can be caused by loss in the functional diversity of MST; first, MST functions as an antioxidant protein. MST possessing 2 redox-sensing molecular switches maintains cellular redox homeostasis. Second, MST can produce H2S (or HS(-)). Third, MST can also produce SOx. It is concluded that behavioral abnormality in MST-KO mice is caused by MST function defects such as an antioxidant insufficiency or a new transducer, H2S (or HS(-)) and/or SOx deficiency.
authors.affiliation: Isotope Research Center, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. noriyuki@nms.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagahara
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nagano
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimamura
authors.forename: Toshio
authors.initials: T
authors.lastname: Akimoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal; D015306:Biogenic Monoamines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D013466:Sulfurtransferases / Q000235:genetics* / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D044282:Receptor, Serotonin, 5-HT1A; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase