Gene expression profiling of oxidative stress on atrial fibrillation in humans

Young Hoon Kim, Ji Hye Lee, Do-Sun Lim, Wan Joo Shim, Young Moo Ro, Gil-Hong Park, Kevin G. Becker, Yoon S. Cho-Chung, Meyoung-Kon Kim

Research output: Contribution to journalArticle

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Abstract

Atrial Fibrillation (AF) is thought be caused by oxidative stress. Oxidative stress at the cellular level results from many factors, including exposure to alcohol, medications, cold, toxins or radiation. In this study we investigated gene transcriptional profiles on the human myocardial tissues from AF and oxidative stress conditions. Right atrial appendages were obtained from AF patients (n = 26) undergoing the Maze procedure, and from control patients (n = 26) who were in normal sinus rhythm and undergoing coronary artery bypass graft operation. To examine the effects of oxidative stress on AF, we used radioactive complementary DNA (cDNA) microarrays to evaluate changes in the expression of 1,152 known genes. This technology, which monitors thousands of genes simultaneously, gives us a better picture of the interactions between AF and oxidative stress. Total RNAs prepared from the retrieved tissues were used to synthesize 33P-labeled cDNAs by reverse transcription and hybridized to cDNA microarrays. Gene expression profiles showed that 30 genes were upregulated and 25 were downregulated in AF patients compared with control patients. Moreover, comparison rank analysis revealed that the expression of five genes related to reactive oxygen species (ROS)-including flavin containing monooxygenase 1, monoamine oxidase B, ubiquitin specific protease 8, tyrosinase-related protein 1, and tyrosine 3-monooxygenase-increased by more than 2.0 of the Z-ratio, and two genes related to antioxidantsincluding glutathione peroxidase 1, and heme oxygenase 2-decreased to the Z-ratio levels of ≤ -2.0. Apparently, a balanced regulation of pro- and anti-oxidation can be shifted toward pro-oxidation and can result in serious damage similar to that of human AF. Western blotting analysis confirmed the upregulation of tyrosinase-related protein 1 and tyrosine 3-monooxygenase and the downregulation of heme oxygenase 2. These results suggested that the gene expression pattern of myocardial tissues in AF patients can be associated with oxidative stress, resulting in a significant increase in ROS. Thus, the cDNA microarray technique was useful for investigating transcription profiles in AF. It showed that the intracellular mechanism of oxidative stress plays a pivotal role in the pathologic progression of AF and offers novel insight into potential treatment with antioxidants.

Original languageEnglish
Pages (from-to)336-349
Number of pages14
JournalExperimental and Molecular Medicine
Volume35
Issue number5
Publication statusPublished - 2003 Oct 31

Fingerprint

Oxidative stress
Gene Expression Profiling
Gene expression
Atrial Fibrillation
Oxidative Stress
Genes
Microarrays
Complementary DNA
Tyrosine 3-Monooxygenase
Oligonucleotide Array Sequence Analysis
Transcription
Tissue
dimethylaniline monooxygenase (N-oxide forming)
Oxidation
Reactive Oxygen Species
Ubiquitin-Specific Proteases
Monoamine Oxidase
Down-Regulation
Grafts
Gene Expression

Keywords

  • Atrial fibrillation
  • cDNA microarray
  • Gene expression profile
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

Gene expression profiling of oxidative stress on atrial fibrillation in humans. / Kim, Young Hoon; Lee, Ji Hye; Lim, Do-Sun; Shim, Wan Joo; Ro, Young Moo; Park, Gil-Hong; Becker, Kevin G.; Cho-Chung, Yoon S.; Kim, Meyoung-Kon.

In: Experimental and Molecular Medicine, Vol. 35, No. 5, 31.10.2003, p. 336-349.

Research output: Contribution to journalArticle

Kim, Young Hoon ; Lee, Ji Hye ; Lim, Do-Sun ; Shim, Wan Joo ; Ro, Young Moo ; Park, Gil-Hong ; Becker, Kevin G. ; Cho-Chung, Yoon S. ; Kim, Meyoung-Kon. / Gene expression profiling of oxidative stress on atrial fibrillation in humans. In: Experimental and Molecular Medicine. 2003 ; Vol. 35, No. 5. pp. 336-349.
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