title: Identification of a novel compound that inhibits both mitochondria-mediated necrosis and apoptosis.
abstract: In various pathological events, particularly in oxygen radical-mediated cell injury, both apoptosis and necrosis play essential roles. Apoptosis and some types of necrosis are induced via increases in mitochondrial membrane permeability, called mitochondrial outer membrane permeabilization (MOMP) and permeability transition pore (PTP) opening, respectively. To search for small compounds that inhibit both MOMP-mediated apoptosis and PTP-mediated necrosis, we performed a mitochondria-based high-throughput screening of a chemical library. We identified TMD#7538, a small compound that inhibits both MOMP and PTP opening. Consistent with the fact that this compound inhibited both apoptosis and necrosis, it efficiently suppressed H2O2-induced cell death in mouse embryonic fibroblasts and rat neonatal cardiomyocytes.
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Arakawa
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Nakanomyo
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kudo-Sakamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. Electronic address: shimizu.pcb@mri.tmd.ac.jp.
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology*; D009336:Necrosis
keywords: Apoptosis; MOMP; Necrosis; PTP; Small compound