Gene expression profiling of oxidative stress on atrial fibrillation in humans
Experimental & Molecular Medicine
;
: 336-349, 2003.
Article
Dans Anglais
| WPRIM
| ID: wpr-171368
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(33)P-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 anti-oxidants including 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Fibrillation auriculaire
/
Régulation de l'expression des gènes
/
Technique de Western
/
Espèces réactives de l'oxygène
/
ADN complémentaire
/
Stress oxydatif
/
Séquençage par oligonucléotides en batterie
/
Auricule de l'atrium
/
Analyse de profil d'expression de gènes
/
Myocarde
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2003
Type:
Article
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