Mode of Action of Oxygen Free Radicals in Excitation-Contraction Coupling System of Masseter Muscle

氧自由基在咬肌兴奋-收缩耦合系统中的作用方式

• 批准号: 03454438
• 负责人: OKABE Eiichiro
• 金额: $ 4.22万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454438/
• 关键词: Masseter muscle; Free radicals; Excitation-contraction coupling; Sarcoplasmic reticulum; Calmodulin; Calcium; Ca^<2+> release channel; カルシウムイオン; 酸素ラジカル; 興奮ー収縮連関; NaーCa交換系; 電子スピン共鳴

In this research project, we wished to investigate 1) Ca^<2+> kinetics, to characterize 2) the route of Ca^<2+> permeability, to define 3) the role of calmodulin in Ca^<2+> fluxes behavior, and to detrmine 4) the effect of acidosis on the excitation-contraction coupling system and 5) the effect of free oxygen radicals using isolated sarcoplasmic reticulum (SR), myofibrils, or the unfractionated homogenate of canine masseter muscle.1. The SR from masseter muscle has greater capability of Ca^<2+> release than that from femoral muscle or heart muscle. The passive Ca^<2+> efflux is not carrier mediated, and is not a likely route of Ca^<2+> release during excitation-contraction coupling.2. Some minimal Ca^<2+> gradient may be required in order to observe a substantial passive Ca^<2+> efflux. It is postulated in this series of research that passive route of efflux during Ca^<2+> accumulation in the SR vesicles is relatively small.3. Calmodulin-dependent process plays a functional role in the coupling of ATP hydrolysis and Ca^<2+> accumulation through regulation of Ca^<2+> release channels in the SR membrane.4. Acidosis significantly uncouples Ca^<2+> transport from ATP hydrolysis in the SR and significantly alters myofibrillar ATPase activity. It is hypothesized that these defects may explain an observed depression in skeletal muscle cell function during ischemia.5. Damage to the masseter muscle is caused by a free radical superoxide anion generated as a result of increased prostaglandins synthesis, and by the production of more lethal hydroxyl radical switched from the production of superoxide anion at low pH.Acidosis can depress SR Ca^<2+> transport in the homogenate of masseter muscle by an oxygen free radical mechanism.

在这个研究项目中，我们希望研究 1) Ca^<2+> 动力学，表征 2) Ca^<2+> 渗透性途径，定义 3) 钙调蛋白在 Ca^<2+> 通量中的作用行为，并确定 4) 酸中毒对兴奋-收缩耦合系统的影响和 5) 使用分离的肌浆网 (SR)、肌原纤维或肌原纤维的自由基的影响犬咬肌普通匀浆。 1．来自咬肌的SR比来自股肌或心肌的SR具有更大的Ca 2+ 释放能力。被动Ca^<2+>流出不是载体介导的，并且不是兴奋-收缩耦合过程中Ca^<2+>释放的可能途径。2．为了观察大量的被动Ca 2+ 流出，可能需要一些最小的Ca 2+ 梯度。本系列研究假设SR囊泡Ca^2+积累过程中被动外流途径相对较小。 3．钙调素依赖性过程通过调节SR膜上的Ca^2+释放通道在ATP水解和Ca^2+积累的耦合中发挥功能性作用。4．酸中毒显着使Ca^2+转运与SR中的ATP水解解偶联，并显着改变肌原纤维ATP酶活性。据推测，这些缺陷可以解释在缺血期间观察到的骨骼肌细胞功能下降。5。咬肌损伤是由前列腺素合成增加产生的自由基超氧阴离子以及低 pH 条件下超氧阴离子产生的更致命的羟基自由基引起的。酸中毒会抑制 SR Ca^<2 +> 通过氧自由基机制在咬肌匀浆中运输。

项目成果

岡部栄逸朗: "心臓-フリーラジカルと心筋酸化ストレス" 現代医療. 25. 3371-3379 (1993)

Eiichiro Okabe：“心脏 - 自由基和心肌氧化应激”现代医学 25. 3371-3379 (1993)。

Todoki K: "Oxygen free radical-mediated selective endothelial dysfunction in isolatedcoronary artery." Am. J.Physiol.262. H806-H812 (1992)

Todoki K：“氧自由基介导的离体冠状动脉选择性内皮功能障碍。”

Eiichiro Okabe: "Aging and oxygen free radical system: possible role in disease in oral region" Bulletin of Kanagawa Dental College. 20. 159-169 (1992)

Eiichiro Okabe：“衰老和氧自由基系统：在口腔区域疾病中的可能作用”神奈川牙科学院通报。

Eiichiro Okabe: "The effect of hypochlorous acid and hydrogen peroxide on coronary flow and arrhythmogenesis in myocardial ischemia and reperfusion" European Journal of Pharmacology. (1993)

Eiichiro Okabe：“次氯酸和过氧化氢对心肌缺血和再灌注中冠状动脉血流和心律失常的影响”《欧洲药理学杂志》。

Nancy M.Manson: "The effect of hypochlorous acid and hydrogen peroxide on coronary flow and arrhythmogenesis in the globally ischemic and reperfused rat heart." J.Mol.Cell.Cardiol.(1992)

Nancy M.Manson：“次氯酸和过氧化氢对全球缺血和再灌注大鼠心脏冠状动脉血流和心律失常的影响。”