Influence of intermittent hypoxia on the signal transduction pathways to inflammatory response and circadian clock regulation
| Autor: | Naoto Burioka, Eiji Shimizu, Shigehiro Ohdo, Satoru Koyanagi, Hisashi Suyama, Hiroki Chikumi, Yasushi Fukuoka, Naoki Kusunose, Fumiyasu Okazaki, Takashi Fujioka, Masahiro Endo |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A medicine.medical_specialty medicine.medical_treatment Circadian clock Inflammation Biology General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Cell Line Tumor Internal medicine medicine Humans RNA Messenger Circadian rhythm General Pharmacology Toxicology and Pharmaceutics Hypoxia Continuous Positive Airway Pressure Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Intermittent hypoxia General Medicine Middle Aged Reference Standards Circadian Rhythm CLOCK Cytokine Endocrinology Gene Expression Regulation Signal transduction medicine.symptom Signal Transduction |
| Zdroj: | Life Sciences. 85:372-378 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2009.07.002 |
| Popis: | Aims 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. Main methods 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. Key findings 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. Significance 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. |
| Databáze: | OpenAIRE |
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