Peroxisome proliferator activated receptor-gamma (PPAR-gamma) mediates the action of gamma linolenic acid in breast cancer cells

Gamma linolenic acid (GLA) is a polyunsaturated fatty acid, which induces cytotoxicity and regulates cell adhesion in cancer cells. The molecular mechanism of these actions is not clear. We have shown that GLA acts via peroxisome proliferator activated receptors (PPARs), by stimulating their phosphorylation and translocation to the nucleus. Removing PPAR gamma with antisense oligos abolished the effect of GLA on the expression of adhesion molecules and tumour suppressor genes, whereas removal of PPAR alpha had no effect. Tissues from patients with breast cancer showed a reduction of expression of both PPARs in cancer tissues, as compared with normal. Thus, PPAR gamma serves as the receptor for GLA in the regulation of gene expression in breast cancer cells.     

PPARs信号通路与哺乳动物生殖

过氧化物酶体增殖因子活化受体(peroxisome proliferator-activated receptors,PPARs)在动物体内有着广泛的生物学作用,可调节脂类代谢、能量收支平衡以及细胞分裂分化等重要生理过程。已经发现,PPARs信号通路与糖尿病和癌症等许多重大疾病的发生有关。随着基因剔除技术的应用以及PPARs人工配体的开发利用,人们对PPARs的认识不断深入。现对PPARs通路在卵巢周期、黄体形成、胚胎着床、胎盘发育和雄性生殖等哺乳动物生殖系统中的表达、功能及作用机制进行综述。     

Fluorescence imaging reveals the nuclear behavior of peroxisome proliferator-activated receptor/retinoid X receptor heterodimers in the absence and presence of ligand

In a global approach combining fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and fluorescence resonance energy transfer (FRET), we address the behavior in living cells of the peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptors involved in lipid and glucose metabolism, inflammation control, and wound healing. We first demonstrate that unlike several other nuclear receptors, PPARs do not form speckles upon ligand activation. The subnuclear structures that may be observed under some experimental conditions result from overexpression of the protein and our immunolabeling experiments suggest that these structures are subjected to degradation by the proteasome. Interestingly and in contrast to a general assumption, PPARs readily heterodimerize with retinoid X receptor (RXR) in the absence of ligand in living cells. PPAR diffusion coefficients indicate that all the receptors are engaged in complexes of very high molecular masses and/or interact with relatively immobile nuclear components. PPARs are not immobilized by ligand binding. However, they exhibit a ligand-induced reduction of mobility, probably due to enhanced interactions with cofactors and/or chromatin. Our study draws attention to the limitations and pitfalls of fluorescent chimera imaging and demonstrates the usefulness of the combination of FCS, FRAP, and FRET to assess the behavior of nuclear receptors and their mode of action in living cells.     

过氧化物酶体增殖物激活受体与动脉粥样硬化

过氧化物酶体增殖物激活受体 (peroxisomeproliferator activatedreceptors ,PPARs)是核受体超家族中的一类配体依赖的核转录因子 ,包括α、β/δ和γ三种亚型 ,在脂肪细胞分化、能量代谢和炎症过程中都发挥重要的作用。最近的研究显示 ,PPARs的活化不仅可以改善包括糖尿病、高血压和肥胖等在内的胰岛素抵抗综合征 ,而且还直接作用于血管壁 ,从而减缓动脉粥样硬化的进程。本综述将就PPARs的结构、功能、与动脉粥样硬化发病机制和治疗相关的最新研究进展进行简要介绍。