Journal
EXPERIMENTAL CELL RESEARCH
Volume 319, Issue 17, Pages 2604-2616Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2013.07.018
Keywords
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha); Ingenuity systems pathway analysis (IPA); Significance analysis of microarrays (SAM); Keshan disease (KD); Immunohistochemical (IHC)
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Funding
- 13115 Major Program on Technology Science Innovation Project of Shaanxi Province [2009ZDKG-79]
- National Natural Scientific Foundation of China [81273008, 30872192]
- Development Program for Science and Technology of Shandong [2008GG10002053]
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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 x 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-1 alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of MD. Our results may lead to the identification of potential diagnostic biomarkers for MD in PBMCs, and may help to understand the pathogenesis of MD. (C) 2013 Elsevier Inc. All rights reserved.
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