个性化文献订阅>期刊> American Journal of Pathology
 

Adiponectin-Mediated Heme Oxygenase-1 Induction Protects Against Iron-Induced Liver Injury via a PPAR alpha-Dependent Mechanism

  作者 Lin, H; Yu, CH; Jen, CY; Cheng, CF; Chou, Y; Chang, CC; Juan, SH  
  选自 期刊  American Journal of Pathology;  卷期  2010年177-4;  页码  1697-1709  
  关联知识点  
 

[摘要]Protective effects of adiponectin (APN; an adipocytokine) were shown against various oxidative challenges; however, its therapeutic implications and the mechanisms underlying hepatic iron overload remain unclear. Herein, we show that the deleterious effects of iron dextran on liver function and iron deposition were significantly reversed by adiponectin gene therapy, which was accompanied by AMP-activated protein kinase (AMPK) phosphorylation and heme oxygenase (HO)-1 induction. Furthermore, AMPK-mediated peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation by APN was ascribable to HO-1 induction. Additionally, we revealed direct transcriptional regulation of HO-1 by the binding of PPAR alpha to a PPAR-responsive element (PPRE) by various experimental assessments. Interestingly, overexpression of HO-1 in hepatocytes mimicked the protective effect of APN in attenuating iron-mediated injury, whereas it was abolished by SnPP and small interfering HO-1. Furthermore, bilirubin, the end-product of the HO-1 reaction, but not CO, protected hepatocytes from iron dextran-mediated caspase activation. Herein, we demonstrate a novel functional PPRE in the promoter regions of HO-1, and APN-mediated HO-1 induction elicited an antiapoptotic effect and a decrease in iron deposition in hepatocytes subjected to iron challenge. (Am J Pathol 2010, 177:1697-1709. DOI: 10.2353/ajpath.2010.090789)

 
      被申请数(0)  
 

[全文传递流程]

一般上传文献全文的时限在1个工作日内