title: Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform.
abstract: Bongkrekic acid (BKA), an antibiotic isolated from Pseudomonas cocovenans, is an inhibitory molecule of adenine nucleotide translocase. Since this translocase is a core component of the mitochondrial permeability transition pore (MPTP) formed by apoptotic stimuli, BKA has been used as a tool to abrogate apoptosis. However, the other biochemical properties of BKA have not yet been resolved. Although the definition of a fatty acid is a carboxylic acid (-COOH) with a long hydrocarbon chain (tail), when focused on the chemical structure of BKA, the molecule was revealed to be a branched unsaturated tricarboxylic acid that resembled the structure of polyunsaturated fatty acids (PUFAs). Peroxisome proliferator-activated receptors (PPARs) consist of a subfamily of three isoforms: α, β, and γ, the ligands of which include PUFAs. Using completely synthesized BKA together with simplified BKA derivatives (purity: > 98%), we herein demonstrated the utility of BKA as a selective activator of the human PPARγ isoform, which may not be associated with the anti-apoptotic nature of BKA. We also discussed the possible usefulness of BKA.
authors: Drug Innovation Research Center, Daiichi University of Pharmacy.
authors: Hiroyuki
authors: H
authors: Okazaki
authors: Shuso
authors: S
authors: Takeda
authors: Eriko
authors: E
authors: Ikeda
authors: Yoshifumi
authors: Y
authors: Fukunishi
authors: Hiroyuki
authors: H
authors: Ishii
authors: Aya
authors: A
authors: Taniguchi
authors: Miki
authors: M
authors: Tokuyasu
authors: Taichi
authors: T
authors: Himeno
authors: Kazuhiro
authors: K
authors: Kakizoe
authors: Kenji
authors: K
authors: Matsumoto
authors: Mitsuru
authors: M
authors: Shindo
authors: Hironori
authors: H
authors: Aramaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis; D001093:Arachidonate 15-Lipoxygenase; D001865:Bongkrekic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors; D047495:PPAR gamma / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D047495:PPAR gamma; D020033:Protein Isoforms; D001865:Bongkrekic Acid; D000226:Mitochondrial ADP, ATP Translocases; D001093:Arachidonate 15-Lipoxygenase