skip to main content

Title: Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy

Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios≥2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD. Highlights:more » • Thirty-four up-regulated genes were detected in KD versus health controls. • Forty pathways and four networks were detected in KD. • PGC-1alpha regulated energy metabolism and anti-apoptosis in KD.« less
Authors:
 [1] ;  [2] ;  [1] ;  [2] ; ;  [1] ;  [2] ;  [3] ; ;  [1] ;  [2] ;  [4] ;  [5] ;
  1. Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi'an, Shaanxi 710061 (China)
  2. (China)
  3. Institute of Biomedicine, University of Eastern Finland, Kuopio (Finland)
  4. Department of Biotechnology, Northwest University, Xi'an, Shaanxi 710069 (China)
  5. Shandong Institute for prevention and Treatment of Endemic Disease, Jinan, Shandong 250014 (China)
Publication Date:
OSTI Identifier:
22278175
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 319; Journal Issue: 17; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; APOPTOSIS; BIOLOGICAL MARKERS; BLOOD; DISEASES; GENES; METABOLISM; MITOCHONDRIA; PATHOGENESIS; RECEPTORS; RNA