Influence of sleep apnea syndrome on clock gene dysfunction

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tottori University
• Principal Investigator: BURIOKA Naoto Tottori University, 医学部, 教授 (50252854)
• Co-Investigator(Renkei-kenkyūsha): CHIKUMI Hiroki 鳥取大学, 医学部, 講師 (90283994) ; SHIMIZU Eiji 鳥取大学, 医学部, 教授 (50187449)
• Project Period (FY): 2008 – 2010
• Keywords: 睡眠時無呼吸症候群 / 間歇的低酸素 / 時計遺伝子 / IL-6 / VEGF

Research Abstract

Obstructive sleep apnea syndrome (OSAS) clinically causes intermittent hypoxia (IH) during sleep. The levels of an inflammation cytokine interleukin-6 (IL-6) mRNA significantly elevated by IH condition in cultured human lung adenocarcinoma epithelial cells (A549), due to activation of the signaling pathway of nuclear factor-KB (NF-KB) which is a potent transcriptional activator of IL-6. However, the treatment of cells with IH had little effect on clock gene expressions. Serum concentrations of IL-6 in OSAS patients were significantly higher than in healthy subjects, but elevated levels of IL-6 in OSAS patients fell to the level of healthy subjects after CPAP therapy. The condition of IH can activate signal transduction to an inflammatory response, but not to circadian clock regulation. The increase of serum IL-6 may cause systemic inflammation in patients with OSAS.

Research Products

• [Journal Article] Asthma : chronopharmacotherapy and the molecular clock. (2010)
  • Author(s): Burioka N, Fukuoka Y, Koyanagi S, Miyata M, Takata M, Chikumi H, Watanabe M, Endo M, Sako T, Suyama H, Ohdo S, Shimizu E.
  • Journal Title: Adv Drug Deliv Rev 62 Pages: 946-955
• [Journal Article] Influence of intermittent hypoxia on the signal transduction pathways to inflammatory response and circadian clock regulation. (2009)
  • Author(s): Burioka N, Koyanagi S, Fukuoka Y, Okazaki F, Fujioka T, Kusunose N, Endo M, Suyama H, Chikumi H, Ohdo S, Shimizu E.
  • Journal Title: Life Sci 85 Pages: 372-378
• [Journal Article] Day-night variations of serum interleukin-6 in patients with severe obstructive sleep apnea syndrome before and after continuous positive airway pressure (CPAP). (2008)
  • Author(s): Burioka N, Miyata M, Endo M, Fukuoka Y, Shimizu E.
  • Journal Title: Chronobiol Int 25 Pages: 827-834
• [Journal Article] Clock gene dysfunction in patients with obstructive sleep apnea syndrome. (2008)
  • Author(s): Burioka N, Koyanagi S, Takata M, Endo M, Fukuoka Y, Miyata M, Takeda K, Chikumi H, Ohdo S, Shimizu E.
  • Journal Title: Eur Respir J 32 Pages: 105-112
• [Presentation] Influence of intermittent hypoxia on the expression of IL-6, VEGF, and clock gene in patients with obstructive sleep apnea syndrome (2009)
  • Author(s): 鰤岡直人, et al.
  • Organizer: 第49回日本呼吸・器学会総会(English mini-symposium)
  • Place of Presentation: 東京国際会議場
  • Year and Date: 2009-06-14
• [Presentation] 閉塞性睡眠時無呼吸症候群に残された臨床的問題点 (2008)
  • Author(s): 鰤岡直人, 他
  • Organizer: 第48回日本呼吸器学会総会(ミニシンポジウム 睡眠呼吸障害)
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-06-16
• [Remarks] ホームページ等
  • URL: http://ww7.enjoy.ne.jp/~nburioka/index.html
• [Patent(Industrial Property Rights)] 生体信号解析装置,生体信号解析方法,生体信号解析プログラム (2010)
  • Inventor(s): 鰤岡直人
  • Industrial Property Rights Holder: 国立大学法人鳥取大学
  • Industrial Property Number: 特許,特願2010-169094
  • Filing Date: 2010-07-28
• [Patent(Industrial Property Rights)] 生体信号解析装置,生体信号解析方法,生体信号解析プログラム (2009)
  • Inventor(s): 鰤岡直人
  • Industrial Property Rights Holder: 国立大学法人鳥取大学
  • Industrial Property Number: 特許,特願2009-244165
  • Filing Date: 2009-10-23