Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform
Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform
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DOI：
10.2131/jts.40.223
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发表时间：
2015-04-01
影响因子：
2
通讯作者：
Aramaki, Hironori
中科院分区：
文献类型：
--
作者：
Okazaki, Hiroyuki;Takeda, Shuso;Aramaki, Hironori
从椰毒假单胞菌中分离得到的一种抗生素BKA是腺嘌呤核苷酸转位酶的抑制分子。由于这种转位酶是由细胞凋亡刺激形成的线粒体通透性转换孔（MPTP）的核心组分，因此BKA已被用作消除细胞凋亡的工具。然而，BKA的其他生化性质尚未得到解决。虽然脂肪酸的定义是具有长烃链（尾部）的羧酸（-COOH），但当关注BKA的化学结构时，该分子被揭示为类似于多不饱和脂肪酸（PUFA）结构的支链不饱和三羧酸。过氧化物酶体增殖物激活受体（PPARs）由三种同种型的亚家族组成：α、β和γ，其配体包括PUFA。使用完全合成的BKA以及简化的BKA衍生物（纯度：> 98%），我们在此证明了BKA作为人PPAR γ同种型的选择性激活剂的效用，这可能与BKA的抗凋亡性质无关。我们还讨论了BKA的可能用途。
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: alpha, beta, 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.