Influence of intermittent hypoxia on the signal transduction pathways to inflammatory response and circadian clock regulation

Obstructive sleep apnea syndrome (OSAS), characterized by intermittent hypoxia/reoxygenation (IHR), is often associated with changing levels of circulating inflammatory cytokines and causes excessive daytime sleepiness, mood disturbances, and cardiovascular disease. An abnormal rhythm in the express...

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Bibliographic Details
Published in:Life sciences (1973) 2009-08, Vol.85 (9), p.372-378
Main Authors: Burioka, Naoto, Koyanagi, Satoru, Fukuoka, Yasushi, Okazaki, Fumiyasu, Fujioka, Takashi, Kusunose, Naoki, Endo, Masahiro, Suyama, Hisashi, Chikumi, Hiroki, Ohdo, Shigehiro, Shimizu, Eiji
Format: Article
Language:English
Subjects:
Adult
Cell Line, Tumor
Circadian rhythm
Circadian Rhythm - genetics
Circadian Rhythm - physiology
Clock gene
Continuous Positive Airway Pressure
Gene Expression Regulation
Humans
Hypoxia - physiopathology
Hypoxia - therapy
IL-6
Interleukin-6 - genetics
Interleukin-6 - metabolism
Intermittent hypoxia/reoxygenation
Male
Middle Aged
Obstructive sleep apnea
Reference Standards
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Signal Transduction
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - metabolism
VEGF
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Summary:Obstructive sleep apnea syndrome (OSAS), characterized by intermittent hypoxia/reoxygenation (IHR), is often associated with changing levels of circulating inflammatory cytokines and causes excessive daytime sleepiness, mood disturbances, and cardiovascular disease. An abnormal rhythm in the expression of circadian clock genes is observed in OSAS patients, and is also implicated in OSAS-related clinical symptoms. IHR-induced signal transduction is thought to underlie OSAS-associated complications. The aim of this study is to elucidate the influence of IHR on signal transduction pathways to inflammatory response and circadian clock regulation. To evaluate the direct action of IHR on intracellular signaling, we used a cell culture model to explore the underlying transcriptional events initiated by IHR. Treatment of cultured human lung adenocarcinoma epithelial cells (A549) with IHR resulted in the elevation of mRNA levels of an inflammation cytokine interleukin-6 (IL-6), due to activation of the signaling pathway of nuclear factor-κB, a potent transcriptional activator of IL-6. On the other hand, the treatment of cells with IHR had little effect on clock gene response element-driven transcription. As a consequence, there was no significant change in mRNA levels of clock genes in IHR-treated cells. These results suggest that IHR can activate signal transduction to an inflammatory response, but not to circadian clock regulation. The abnormal rhythm in the expression of clock genes in OSAS patients is attributable to the changed levels of circulating factors that have the ability to modulate clock gene expression.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2009.07.002