The ligands/activators for peroxisome proliferator-activated receptor α (PPARα) and PPARγ increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells
The ligands/activators for peroxisome proliferator-activated receptor α (PPARα) and PPARγ increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells
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DOI：
10.1053/meta.2001.19415
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发表时间：
2001-01-01
影响因子：
9.8
通讯作者：
Katayama, S
中科院分区：
文献类型：
--
作者：
Inoue, I;Goto, S;Katayama, S
在原代培养的人脐静脉内皮细胞(HUVEC)和人主动脉内皮细胞(HAEC)中，观察了过氧化物酶体增殖物激活受体(PPAR)的不同配体/激活剂对超氧化物歧化酶Cu2+，Zn2+-超氧化物歧化酶(CuZN-SOD)和超氧化物产生酶烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶表达的影响。我们的数据显示，内皮细胞表达三种类型的PPAR，即PPARα、PPARβ/Delta Nuc1和PPAR Gamma。苯扎贝特是PPARα的配体/激活剂，它增加了内皮细胞CuZn-SOD基因的表达和蛋白水平。曲格列酮和吡格列酮作为PPARγ的配体/激活剂，除了增加PPARγ基因和蛋白的表达外，还能诱导PPARα基因和蛋白的表达，并增加CuZn-SOD基因和蛋白的表达水平。此外，在单不饱和脂肪酸和多不饱和脂肪酸(PUFA)处理下，原代内皮细胞CuZn-SOD的mRNA水平与PPARα的mRNA水平呈正相关(r=0.872，P<；0.0001)。此外，PPAR和PPARγ配体/激活剂均能降低PPAR和PPARγ配体/激活剂对NADPH氧化酶中PMA刺激或非刺激的22kd a亚基(P22Phox)mRNA和47kd a亚单位(P47Phox)蛋白水平的影响。这些结果表明，内皮细胞中PPARα和PPARγ基因和蛋白的表达可能作为自由基清除剂发挥了生理学作用，但这些机制的细节仍有待确定。版权所有(C)2001，由W.B.Saunders公司提供。
We examined the effects of a variety of ligands/activators of the peroxisome proliferator-activated receptor (PPAR) on the expression of the superoxide scavenger enzyme, Cu2+, Zn2+-superoxide dismutase (CuZn-SOD), and the superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase in primary cultures of human umbilical vein endothelial cells (HUVEC) and human aorta endothelial cells (HAEC). Our data show that 3 types of PPARs, PPAR alpha, PPAR beta/delta Nuc1, and PPAR gamma are expressed in endothelial cells. Bezafibrate, which is a ligand/activator for PPAR alpha, increased the CuZn-SOD gene expression and protein levels in endothelial cells. Troglitazone and pioglitazone, which are ligands/activators for PPAR gamma, also induced PPAR alpha gene and protein expression and increased CuZn-SOD gene expression and protein levels in addition to increasing PPAR gamma gene and protein expression in endothelial cells. Moreover, with treatment of monounsaturated and polyunsaturated fatty acids (PUFA), the CuZn-SOD mRNA levels were positively correlated with PPAR alpha mRNA levels (r = .872, P < .0001) in primary endothelial cells. In addition, the phorbol myristate acetate (PMA)-stimulated or PMA-nonstimulated 22-kd a-subunit (p22phox) mRNA levels and 47-kd a-subunit (p47phox) protein levels in NADPH oxidase were decreased by treatment with PPAR and PPAR gamma ligands/activators. These results suggest that PPAR alpha and PPAR gamma gene and protein expression in endothelial cells may play a physiologic role as radical scavengers, although the details of these mechanisms remain to be established. Copyright (C) 2001 by W.B. Saunders Company.