Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) isoform

• Published in: Journal of toxicological sciences 2015-03, Vol.40 (2), p.223
• Main Authors: Okazaki, Hiroyuki, Takeda, Shuso, Ikeda, Eriko, Fukunishi, Yoshifumi, Ishii, Hiroyuki, Taniguchi, Aya, Tokuyasu, Miki, Himeno, Taichi, Kakizoe, Kazuhiro, Matsumoto, Kenji, Shindo, Mitsuru, Aramaki, Hironori
• Format: Article
• Language: English
• ISSN: 0388-1350; 1880-3989

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 [gamma], 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 PPAR[gamma] isoform, which may not be associated with the anti-apoptotic nature of BKA. We also discussed the possible usefulness of BKA.