2001 Fiscal Year Annual Research Report

マクロファージをプローブとした肥満と免疫機構の解析

Research Project

Project/Area Number	12670328
Research Institution	Kyorin University
Principal Investigator	木崎節子杏林大学, 医学部, 助教授 (00322446)
Keywords	UCP-2 / マクロファージ / NOSII / 活性酸素 / 肥満 / 転写調節 / イントロン / LPS
Research Abstract	糖尿病、高血圧、動脈硬化など、肥満が危険因子となる疾病には一酸化窒素(NO)を介したマクロファージの関与が考えられている。一方、脱共役タンパク質2(UCP-2)は、マクロファージなどの免疫系組織での発現が強く、活性酸素の産生を調節することが示唆されている。本研究では、マクロファージのNO産生調節におけるUCP-2の関与を検討した。LPS刺激により、マクロファージでUCP-2のmRNA及びタンパク質の発現量の低下がみられた。UCP-2発現低下の生理的意義を明らかにするために、UCP-2過剰発現細胞株(RAW264ucp2)を樹立した。このRAW264ucp2細胞では、1)LPS刺激による細胞内活性酸素産生量増加の消失、2)NO産生能、誘導型NO合成酵素(NOSII)のタンパク質とmRNAの発現量、及びNOSIIpromoterの転写活性の低下が認められた。UCP-2の転写調節機構をレポーターアッセイにより解析した結果、promoter領域の3'側約200bp領域に高い転写活性を認めたが、LPS刺激によるレポーター遺伝子の発現抑制はみられなかった。一方、promoter領域に加えてUCP-2遺伝子の5'側非翻訳領域の配列を挿入したconstructで、LPS刺激後明らかな発現抑制が認められた。さらに、LPSによるUCP-2の発現抑制は2番目のintronを欠損させることで消失した。以上の結果から、LPS刺激によるUCP-2の発現低下は、活性酸素を増加させることでNO産生の情報伝達系の活性化に関与しており、その調節作用は2番目のintron領域に起因していることが示唆された。このUCP-2発現調節機構の存在は、迅速なLPS応答に重要な役割を果たしているものと考えられる。

Research Products

(34 results)

All Other

All Publications (34 results)

[Publications] Kizaki, T.: "Age-associated increase of basal corticosterone levels decreases ED2high, NF-kappaBhigh activated macrophages"J.Leukocyte Biol.. 68・1. 21-30 (2000)
[Publications] Kizaki, T.: "Effects of ageing on generation of ED2high major hist compatibility complex classII+macrophages during cold stress"Scand.J.Immunol.. 51・1. 36-44 (2000)
[Publications] Kizaki, T.: "Swimming training prevents generation of suppressor macrophages during acute cold stress"Med.Sci.Sports Exerc.. 32・1. 143-148 (2000)
[Publications] Nakao, C.: "Extracellular superoxide dismutase in tissues from obese (ob/ob) mice"Free Radic.Res. 33・3. 229-241 (2000)
[Publications] Nakao, C.: "Effects of swimming training on three superoxide dismutase isoenzymes in mouse tissues"J.Appl.Physiol.. 88・2. 649-654 (2000)
[Publications] Izawa, T.: "Inhibition of adipocyte lipolysis by papaberine : Papaberine can inhibit the redistribution of hormone-sensitive lipase"Life Sci.. 66・25. 359-364 (2000)
[Publications] Harada, M.: "Mercury pollution in the Tapajos River basin, Amazon : mercury level of head hair and health effects"Environ Int.. 27・4. 285-290 (2001)
[Publications] 大野秀樹: "運動とフリーラジカル"体力科学. 50・4. 389-416 (2001)
[Publications] 木崎節子: "マクロファージの一酸化窒素産生制御機構"運動生化学. 11/12. 67-73 (2001)
[Publications] 大河原知水: "核移行型extracellular superoxide dismutase(EC-SOD)の解析"運動生化学. 11/12. 39-41 (2001)
[Publications] 大野秀樹: "遺伝子から見た高所医学"登山医学. 21. 7-12 (2001)
[Publications] Kizaki, T.: "Stress-and aging-associated modulation of macrophage functions"Environ.Health Prev. Med.. 6・4. 218-228 (2002)
[Publications] Ookawara, T.: "Serum extracellular superoxide dismutase in pediatric patients with various diseases as judged by an ELISA"Res.Commun.Mol.Pathol.Pharmacol.. 107・3-4. 291-296 (2000)
[Publications] Bae, S.Y.: "Quantitative contribution of oxidative metabolism in the human calf during supramaximal planter flexion exercise"Adv.Exerc.Sports Physiol.. 6・1. 7-16 (2000)
[Publications] Toshinai, K.: "Effects of different intensity and duration of exercise with the same oxygen consumption on the ability of neutrophils to generate superoxide anion radical in man"Adv.Exerc.Sports Physiol.. 6・3. 91-95 (2000)
[Publications] Miyazaki, H.: "The synergistic effect of dietary calcium restriction and exhaustive exercise on the antioxidant enzyme system in rat heart"Adv.Exerc.Sports Physiol.. 6・3. 85-89 (2000)
[Publications] 大野秀樹: "活性酸素と運動"呼吸と循環. 48・8. 761-767 (2000)
[Publications] 大野秀樹: "特集慢性呼吸器疾患のQOR-生命予後の延長からQOLの向上まで-基礎医学とのダイアローグ運動と活性酸素とライフスタイル"THE LUNG perspectives. 8・4. 493-497 (2000)
[Publications] 大野秀樹: "身体活動と活性酸素"日本臨床. 58(増刊号). 77-81 (2000)
[Publications] Kizaki, T.: "Activation and apoptosis of murine peritoneal macophages by acute cold stress"Biochem.Biophys.Res.Commun.. 283・3. 700-706 (2001)
[Publications] Kizaki, T.: "Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase byAP-1 in macrophage cell line J774A.1"Biochem.Biophys.Res.Commun.. 289・5. 1031-1038 (2001)
[Publications] Harada, M.: "Wide use of skin-lightening soap may cause mercury poisoning in Kenya"Sci.Total Environ.. 269・1-3. 183-187 (2001)
[Publications] Miyazaki, H.: "Strenous endurance training reduces oxidative stress following exhaustive exercise"Eur.J.Appl.Physiol.. 84・1-2. 1-6 (2001)
[Publications] Saitoh, D.: "Changes in the tissue and plasma superoxide dismutase (SOD) levels in a burned rat model"Tohoku J.Exp.Med.. 193・1. 27-36 (2001)
[Publications] Ito, Y.: "Exercise training increases membrane bound form of tumor necrosis factor-a receptors with decreases in the secretion of soluble forms of receptors in rat adipocytes"Life Sci.. (in press). (2002)
[Publications] Suzuki, K.: "Handbook of Oxidants and Antioxidants in Exercise"Elsevier. 52 (2000)
[Publications] 大野秀樹: "運動生理学的基礎と応用"ナップ. 9 (2000)
[Publications] Oh-ishi, S.: "Free Radicals in Exercise and Aging"Human Kinetics. 47 (2000)
[Publications] 大野秀樹: "登山の医学ハンドブック"杏林書院. 4 (2000)
[Publications] 大野秀樹: "身体運動・栄養・健康の生命科学Q&A骨格筋と運動"杏林書院. 2 (2001)
[Publications] 木崎節子: "運動とホルモン-液性因子による調節と適応-"ナップ. 22 (2001)
[Publications] 木崎節子: "運動生理・生化学辞典"大修館書店. 6 (2001)
[Publications] 鈴木健二: "医学研究のためのテクニカルガイダンス"メディカルレビュー社. 42 (2001)
[Publications] 木崎節子: "Q&A運動と遺伝"大修館書店. 6 (2001)

2001 Fiscal Year Annual Research Report

マクロファージをプローブとした肥満と免疫機構の解析

Principal Investigator

木崎 節子 杏林大学, 医学部, 助教授 (00322446)

Research Products

[Publications] Kizaki, T.: "Age-associated increase of basal corticosterone levels decreases ED2high, NF-kappaBhigh activated macrophages"J.Leukocyte Biol.. 68・1. 21-30 (2000)

[Publications] Kizaki, T.: "Effects of ageing on generation of ED2high major hist compatibility complex classII+macrophages during cold stress"Scand.J.Immunol.. 51・1. 36-44 (2000)

[Publications] Kizaki, T.: "Swimming training prevents generation of suppressor macrophages during acute cold stress"Med.Sci.Sports Exerc.. 32・1. 143-148 (2000)

[Publications] Nakao, C.: "Extracellular superoxide dismutase in tissues from obese (ob/ob) mice"Free Radic.Res. 33・3. 229-241 (2000)

[Publications] Nakao, C.: "Effects of swimming training on three superoxide dismutase isoenzymes in mouse tissues"J.Appl.Physiol.. 88・2. 649-654 (2000)

[Publications] Izawa, T.: "Inhibition of adipocyte lipolysis by papaberine : Papaberine can inhibit the redistribution of hormone-sensitive lipase"Life Sci.. 66・25. 359-364 (2000)

[Publications] Harada, M.: "Mercury pollution in the Tapajos River basin, Amazon : mercury level of head hair and health effects"Environ Int.. 27・4. 285-290 (2001)

[Publications] 大野秀樹: "運動とフリーラジカル"体力科学. 50・4. 389-416 (2001)

[Publications] 木崎節子: "マクロファージの一酸化窒素産生制御機構"運動生化学. 11/12. 67-73 (2001)

[Publications] 大河原知水: "核移行型extracellular superoxide dismutase(EC-SOD)の解析"運動生化学. 11/12. 39-41 (2001)

[Publications] 大野秀樹: "遺伝子から見た高所医学"登山医学. 21. 7-12 (2001)

[Publications] Kizaki, T.: "Stress-and aging-associated modulation of macrophage functions"Environ.Health Prev. Med.. 6・4. 218-228 (2002)

[Publications] Ookawara, T.: "Serum extracellular superoxide dismutase in pediatric patients with various diseases as judged by an ELISA"Res.Commun.Mol.Pathol.Pharmacol.. 107・3-4. 291-296 (2000)

[Publications] Bae, S.Y.: "Quantitative contribution of oxidative metabolism in the human calf during supramaximal planter flexion exercise"Adv.Exerc.Sports Physiol.. 6・1. 7-16 (2000)

[Publications] Toshinai, K.: "Effects of different intensity and duration of exercise with the same oxygen consumption on the ability of neutrophils to generate superoxide anion radical in man"Adv.Exerc.Sports Physiol.. 6・3. 91-95 (2000)

[Publications] Miyazaki, H.: "The synergistic effect of dietary calcium restriction and exhaustive exercise on the antioxidant enzyme system in rat heart"Adv.Exerc.Sports Physiol.. 6・3. 85-89 (2000)

[Publications] 大野秀樹: "活性酸素と運動"呼吸と循環. 48・8. 761-767 (2000)

[Publications] 大野秀樹: "特集 慢性呼吸器疾患のQOR-生命予後の延長からQOLの向上まで-基礎医学とのダイアローグ 運動と活性酸素とライフスタイル"THE LUNG perspectives. 8・4. 493-497 (2000)

[Publications] 大野秀樹: "身体活動と活性酸素"日本臨床. 58(増刊号). 77-81 (2000)

[Publications] Kizaki, T.: "Activation and apoptosis of murine peritoneal macophages by acute cold stress"Biochem.Biophys.Res.Commun.. 283・3. 700-706 (2001)

[Publications] Kizaki, T.: "Negative regulation of LPS-stimulated expression of inducible nitric oxide synthase byAP-1 in macrophage cell line J774A.1"Biochem.Biophys.Res.Commun.. 289・5. 1031-1038 (2001)

[Publications] Harada, M.: "Wide use of skin-lightening soap may cause mercury poisoning in Kenya"Sci.Total Environ.. 269・1-3. 183-187 (2001)

[Publications] Miyazaki, H.: "Strenous endurance training reduces oxidative stress following exhaustive exercise"Eur.J.Appl.Physiol.. 84・1-2. 1-6 (2001)

[Publications] Saitoh, D.: "Changes in the tissue and plasma superoxide dismutase (SOD) levels in a burned rat model"Tohoku J.Exp.Med.. 193・1. 27-36 (2001)

[Publications] Ito, Y.: "Exercise training increases membrane bound form of tumor necrosis factor-a receptors with decreases in the secretion of soluble forms of receptors in rat adipocytes"Life Sci.. (in press). (2002)

[Publications] Suzuki, K.: "Handbook of Oxidants and Antioxidants in Exercise"Elsevier. 52 (2000)

[Publications] 大野秀樹: "運動生理学的基礎と応用"ナップ. 9 (2000)

[Publications] Oh-ishi, S.: "Free Radicals in Exercise and Aging"Human Kinetics. 47 (2000)

[Publications] 大野秀樹: "登山の医学ハンドブック"杏林書院. 4 (2000)

[Publications] 大野秀樹: "身体運動・栄養・健康の生命科学Q&A骨格筋と運動"杏林書院. 2 (2001)

[Publications] 木崎節子: "運動とホルモン-液性因子による調節と適応-"ナップ. 22 (2001)

[Publications] 木崎節子: "運動生理・生化学辞典"大修館書店. 6 (2001)

[Publications] 鈴木健二: "医学研究のためのテクニカルガイダンス"メディカルレビュー社. 42 (2001)

[Publications] 木崎節子: "Q&A運動と遺伝"大修館書店. 6 (2001)

木崎節子杏林大学, 医学部, 助教授 (00322446)

[Publications] 大野秀樹: "特集慢性呼吸器疾患のQOR-生命予後の延長からQOLの向上まで-基礎医学とのダイアローグ運動と活性酸素とライフスタイル"THE LUNG perspectives. 8・4. 493-497 (2000)