Aldose reductase regulates hepatic peroxisome proliferator-activated receptor alpha phosphorylation and activity to impact lipid homeostasis

CORC > 厦门大学 > 化学化工－已发表论文

	Aldose reductase regulates hepatic peroxisome proliferator-activated receptor alpha phosphorylation and activity to impact lipid homeostasis
	Qiu, Longxin ; Wu, Xiaochun ; Chau, Jenny F. L. ; Szeto, Irene Y. Y. ; Tam, Wing Yip ; Guo, Zongsheng ; Chung, Sookja K. ; Oates, Peter J. ; Chung, Stephen S. M. ; Yang, James Y. ; Yang CY(杨朝勇)
刊名	http://dx.doi.org/10.1074/jbc.M801791200
	2008-06-20
关键词	PROTEIN-KINASE-C PPAR-ALPHA POLYOL PATHWAY DIABETIC COMPLICATIONS DEFICIENT MICE HIGH GLUCOSE HUMAN-LIVER METABOLISM EXPRESSION GENE
英文摘要	Aldose reductase (AR) is implicated in the development of a number of diabetic complications, but the underlying mechanisms remain to be fully elucidated. We performed this study to determine whether and how AR might influence hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha) activity and lipid metabolism. Our results in mouse hepatocyte AML12 cells show that AR overexpression caused strong suppression of PPAR alpha/delta activity (74%, p < 0.001) together with significant down-regulation of mRNA expression for acetyl-CoA oxidase and carnitine palmitoyltransferase-1. These suppressive effects were attenuated by the selective AR inhibitor zopolrestat. Furthermore, AR overexpression greatly increased the levels of phosphorylated PPAR alpha and ERK1/2. Moreover, AR-induced suppression of PPAR alpha activity was attenuated by treatment with an inhibitor for ERK1/2 but not that for phosphoinositide 3-kinase, p38, or JNK. Importantly, similar effects were observed for cells exposed to 25 mM glucose. In streptozotocin-diabetic mice, AR inhibitor treatment or genetic deficiency of AR resulted in significant dephosphorylation of both PPAR alpha and ERK1/2. With the dephosphorylation of PPAR alpha, hepatic acetyl-CoA oxidase and apolipoprotein C-III mRNA expression was greatly affected and that was associated with substantial reductions in blood triglyceride and nonesterified fatty acid levels. These data indicate that AR plays an important role in the regulation of hepatic PPAR alpha phosphorylation and activity and lipid homeostasis. A significant portion of the AR-induced modulation is achieved through ERK1/2 signaling.
语种	英语
出版者	J BIOL CHEM
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/88595]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Qiu, Longxin,Wu, Xiaochun,Chau, Jenny F. L.,et al. Aldose reductase regulates hepatic peroxisome proliferator-activated receptor alpha phosphorylation and activity to impact lipid homeostasis[J]. http://dx.doi.org/10.1074/jbc.M801791200,2008.
APA	Qiu, Longxin.,Wu, Xiaochun.,Chau, Jenny F. L..,Szeto, Irene Y. Y..,Tam, Wing Yip.,...&杨朝勇.(2008).Aldose reductase regulates hepatic peroxisome proliferator-activated receptor alpha phosphorylation and activity to impact lipid homeostasis.http://dx.doi.org/10.1074/jbc.M801791200.
MLA	Qiu, Longxin,et al."Aldose reductase regulates hepatic peroxisome proliferator-activated receptor alpha phosphorylation and activity to impact lipid homeostasis".http://dx.doi.org/10.1074/jbc.M801791200 (2008).