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

Okazaki Hiroyuki; Takeda Shuso; Ikeda Erika; Fukunishi Yoshifumi; Ishii Hiroyuki; Taniguchi Aya; Tokuyasu Miki; Himeno Taichi; Kakizoe Kazuhiro; Matsumoto Kenji; Shindo Mitsuru; Aramaki Hironori

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

机译：奉克酸作为过氧化物酶体增殖物激活受体γ（PPARγ）亚型的选择性激活剂

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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.

机译：凤梨酸（BKA）是一种从椰子假单胞菌分离的抗生素，是腺嘌呤核苷酸转位酶的抑制分子。由于这种转位酶是由凋亡刺激形成的线粒体通透性过渡孔（MPTP）的核心成分，因此BKA已被用作消除细胞凋亡的工具。但是，BKA的其他生化特性尚未解决。尽管脂肪酸的定义是具有长烃链（尾）的羧酸（-COOH），但当着眼于BKA的化学结构时，发现该分子为支链不饱和三羧酸，类似于多不饱和结构脂肪酸（PUFA）。过氧化物酶体增殖物激活受体（PPAR）由三个亚型的亚家族组成：α，β和γ，其配体包括PUFA。使用完全合成的BKA和简化的BKA衍生物（纯度：> 98％），我们在本文中证明了BKA作为人PPARγ亚型的选择性激活剂的效用，它可能与BKA的抗凋亡性质无关。我们还讨论了BKA的可能用途。

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《The Journal of toxicological sciences》 |2015年第2期|共11页
作者
Okazaki Hiroyuki; Takeda Shuso; Ikeda Erika; Fukunishi Yoshifumi; Ishii Hiroyuki; Taniguchi Aya; Tokuyasu Miki; Himeno Taichi; Kakizoe Kazuhiro; Matsumoto Kenji; Shindo Mitsuru; Aramaki Hironori;
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正文语种 eng
中图分类药学;
关键词
Bongkrekic acid; Peroxisome proliferator-activated receptor gamma; Adenine nucleotide translocase; 15-Lipoxygenase; Apoptosis;

机译：奉克酸;过氧化物酶体增殖物激活受体γ;腺嘌呤核苷酸转位酶;15-脂氧合酶;凋亡;

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1. Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor gamma (PPAR gamma) isoform [J] . Okazaki Hiroyuki, Takeda Shuso, Ikeda Erika, The Journal of toxicological sciences . 2015,第2期

机译：奉克酸作为过氧化物酶体增殖物激活受体γ（PPARγ）亚型的选择性激活剂
2. Argan oil prevents down-regulation induced by endotoxin on liver fatty acid oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor gamma coactivator-1α, (PGC-1α), peroxisome proliferator-activated receptor α (PPARα) and estrogen r [J] . Riad El Kebbaj, Pierre Andreoletti, Hammam I. El Hajj, Biochimie Open . 2015,第3期

机译：摩洛哥坚果油可防止内毒素引起的肝脏脂肪酸氧化和糖异生以及过氧化物酶体增殖物激活受体γcoactivator-1α（PGC-1α），过氧化物酶体增殖物激活受体α（PPARα）和雌激素的下调
3. Conjugated linoleic acid is an activator and ligand for peroxisome proliferator-activated receptor-gamma (PPAR gamma) [J] . Belury MA, Moya-Camarena SY, Lu M, Nutrition Research . 2002,第7期

机译：共轭亚油酸是过氧化物酶体增殖物激活受体-γ（PPAR gamma）的激活剂和配体
4. α-Naphtyl Substituted Pirinixic Acid Derivatives as Potent Selective Agonists of the Peroxisome Proliferator-Activated Receptor Gamma [C] . Theresa M. Thieme, Ramona Steri, Ewgenij Proschak European Symposium on Organic Chemistry . 2009

机译：α-萘基取代的吡啶酸衍生物作为过氧化物体增殖物激活的受体γ的有效选择性激动剂
5. Peroxisome proliferator-activated receptor gamma (PPARgamma)-independent antitumor effect of thiazolidinediones. [D] . Wei, Shuo. 2010

机译：噻唑烷二酮类药物的过氧化物酶体增殖物激活受体γ（PPARgamma）独立的抗肿瘤作用。
6. Argan oil prevents down-regulation induced by endotoxin on liver fatty acid oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) peroxisome proliferator-activated receptor α (PPARα) and estrogen related receptor α (ERRα) [O] . Riad El Kebbaj, Pierre Andreoletti, Hammam I. El Hajj, 2015

机译：摩洛哥坚果油可防止内毒素引起的肝脏脂肪酸氧化和糖异生以及过氧化物酶体增殖物激活受体γcoactivator-1α（PGC-1α）过氧化物酶体增殖物激活受体α（PPARα）和雌激素相关受体α（ERRα）的下调。）
7. Argan oil prevents down-regulation induced by endotoxin on liver fatty acid oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor gamma coactivator-1α, (PGC-1α), peroxisome proliferator-activated receptor α (PPARα) and estrogen related receptor α (ERRα) [O] . Riad El Kebbaj, Pierre Andreoletti, Hammam I. El Hajj, 2015

机译：摩洛哥坚果油防止内毒素对肝脏脂肪酸氧化和糖异生诱导的下调和过氧化物酶体增殖物激活受体γ辅激活物-1α（pGC-1α），过氧化物酶体增殖物激活受体α（ppaRα）和雌激素相关受体α（ERRα）的下调）
8. Defining the Molecular Actions of Dietary Fatty Acids in Breast Cancer: Selective Modulation of Peroxisome Proliferator-Activated Receptor Gamma. Addendum; Final rept. 30 Sep 2006-8 Apr 2008 [R] . Allred, C. D., Kilgore, M. W. 2008

机译：定义膳食脂肪酸在乳腺癌中的分子作用：过氧化物酶体增殖物激活的受体γ的选择性调节。附录;最终的评论。 2006年9月30日至2008年4月8日

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

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