Zhu Y, Alvares K, Huang Q, Rao M S, Reddy J K
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
J Biol Chem. 1993 Dec 25;268(36):26817-20.
Peroxisome proliferators are postulated to elicit predictable pleiotropic responses in the liver by activating a peroxisome proliferator-activated receptor (PPAR). PPARs from mouse liver (mPPAR), rat liver (rPPAR), and Xenopus liver (xPPAR gamma) have been cloned recently. We now report the cloning of a new member from mouse liver which we designate mPPAR gamma. mPPAR gamma cDNA contained an open reading frame encoding a 475-amino acid protein exhibiting 75% amino acid similarity to xPPAR gamma, while it showed only 55% identity with mPPAR. The ligand-binding and DNA-binding domains are best conserved between mPPAR gamma, mPPAR, and xPPAR gamma. Like rPPAR, mPPAR gamma is able to impart peroxisome proliferator responsiveness to the promoter of peroxisomal bifunctional gene, which encodes the second enzyme of the peroxisomal fatty acid beta-oxidation system. Northern blot analysis revealed high expression of mPPAR gamma gene in mouse liver, kidney, and heart and low expression in the lung, testis, brain, skeletal muscle, and spleen. In mice treated with ciprofibrate, a peroxisome proliferator, a 2-fold increase in mPPAR gamma mRNA was observed in the liver and kidney. The presence of two PPARs in the mouse liver suggests the possibility of multiple signaling pathways for the peroxisome proliferator-induced pleiotropic responses.
过氧化物酶体增殖剂被假定通过激活过氧化物酶体增殖剂激活受体（PPAR）在肝脏中引发可预测的多效性反应。来自小鼠肝脏（mPPAR）、大鼠肝脏（rPPAR）和非洲爪蟾肝脏（xPPARγ）的PPARs最近已被克隆。我们现在报告从小鼠肝脏中克隆出一个新成员，我们将其命名为mPPARγ。mPPARγ cDNA包含一个开放阅读框，编码一种475个氨基酸的蛋白质，与xPPARγ的氨基酸相似性为75%，而与mPPAR的同一性仅为55%。mPPARγ、mPPAR和xPPARγ之间的配体结合域和DNA结合域保守性最佳。与rPPAR一样，mPPARγ能够赋予过氧化物酶体增殖剂对过氧化物酶体双功能基因启动子的反应性，该基因编码过氧化物酶体脂肪酸β-氧化系统的第二种酶。Northern印迹分析显示，mPPARγ基因在小鼠肝脏、肾脏和心脏中高表达，在肺、睾丸、脑、骨骼肌和脾脏中低表达。在用过氧化物酶体增殖剂环丙贝特处理的小鼠中，肝脏和肾脏中的mPPARγ mRNA增加了2倍。小鼠肝脏中存在两种PPARs，这表明过氧化物酶体增殖剂诱导的多效性反应可能存在多种信号通路。
