title: Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.
abstract: We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain.
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Ishibashi
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Saiki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Kyoshiro
authors.initials: K
authors.lastname: Kuni
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. Electronic address: iga16077@faculty.chiba-u.jp.
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
mesh_terms: D000171:Acrolein / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D000097667:Polyamine Oxidase
chemical_list: D000171:Acrolein; D005978:Glutathione; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000097667:Polyamine Oxidase
keywords: Aging; Brain infarction; Glutathione; Protein-conjugated acrolein; Spermine oxidase