Research on cell injury due to Carbon Monoxide and Nitric Oxide under ischemia or shock

缺血或休克时一氧化碳和一氧化氮所致细胞损伤的研究

• 批准号: 14370152
• 负责人: YOSHIDA Ken-ichi
• 金额: $ 9.73万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370152/
• 关键词: Carbon Monoxide; Nitric Oxide; Myocardium; Ischemia; Reperfusion; NO syntase; Reactive Oxygen; Species Calcium; 一酸化炭素(CO); 虚血性心疾患; 遅発脳障害; 脂質過酸化; 細胞死; 虚血再灌流; 活性酸素; 心臓; 血管内皮; 細胞内情報伝達; Carbon Monoxide; Nitric Oxide; Myocardium; Ischemia; Reperfusion; NO syntase; Reactive Oxygen; Species Calcium; 一酸化炭素(CO); 虚血性心疾患; 遅発脳障害; 脂質過酸化; 細胞死; 虚血再灌流; 活性酸素; 心臓; 血管内皮; 細胞内情報伝達

Heme-oxygenase (HO)-1, generates CO, thereby protecting the cells. We have shown that a Ca^<2+>-dependent protease calpain promotes necrotic death in the cardiogenic H9c2 cells under hypoxia through α-fodrin proteolysis. The Ca^<2+>-influx, α-fodrin proteolysis and schemic death, were inhibited by CO or L-type Ca^<2+>-channel inhibitor verapamil. Ischemia also induced mitochondrial depolarization, which was inhibited by CO or verapamil. HO-1 induction reduced the Ca^<2+>-influx and cell death after ischemia. Thus, exogenous and endogenous CO protect the cardiomyogenic cells against ischemia by inhibiting Ca^<2+>-influx through L-type Ca^<2+> channel and calpain activation.After short (15, 30 min) and long (45, 60 min) time. of ischemia by coronary artery occlusion of the rats, reperfusion caused dilatation and constriction of arterioles, respectively. The vascular diameter was correlated with enhanced immunofluorescence for Akt and phosphorylated forms of serine 1177 residue 鋲NOS, and NO-bound form of guanylate cyclase (GC), as confirmed by western blotting. The constriction during reperfusion after 45 min of ischemia is related to the inhibition of Akt-mediated eNOS-Ser1177 phosphorylation, which was suppressed by a PKC inhibitor chelerythrine, a flavoprotein inhibitor DPI, or reactive oxygen species (ROS) scavengers MPG and Tiron. An endothelin receptor antagonist BQ123 alleviated the vasoconstriction by increasing NO availability but not eNOS phosphorylation. Thus, vascular patency correlated with eNOS-Ser1177 phosphorylation during ischemia-ieperfusion, and is affecled by ROS, PKC, and flavoproteins.

血红素 - 氧合酶（HO）-1生成CO，从而保护细胞。 We have shown that a Ca^<2+>-dependent proteinase calpain promotes necrotic death in the cardiogenic H9c2 cells under hypoxia through α-fodrin proteinolysis. CA^<2+> - 流入，α-佛教蛋白蛋白解和精神分裂死亡，被CO或L型Ca^<2+> - 通道抑制剂Verapamil抑制。缺血还诱导线粒体沉积，该沉积被CO或Verapamil抑制。 HO-1诱导减少了缺血后的Ca^<2+> - 流入和细胞死亡。这是通过抑制Ca^<2+> - 通过L型Ca^<2+>通道和钙蛋白酶激活来保护心肌细胞免受缺血保护的外源和内源性CO。大鼠的冠状动脉阻塞缺血，再灌注引起动脉的膨胀和收缩，血管直径与Akt的免疫荧光增强与Akt的免疫荧光相关，而丝氨酸的丝氨酸形式和丝氨酸1177保留NOS的磷酸化形式是保留NOS的NOS，并没有由近甲基酸酯循环酶（GC）确认。缺血45分钟后再灌注期间的收缩与抑制Akt介导的eNOS-SER1177磷酸化有关，该磷酸化被PKC抑制剂螯合剂抑制，黄叶蛋白抑制剂DPI或反应性氧气（ROS）氧化物（ROS）Scavengers（ROS）Scavengers（ROS）。内皮素受体拮抗剂BQ123通过增加没有可用性但没有eNOS磷酸化来缓解血管收缩。这是缺血期间的eNOS-SER1177磷酸化的血管通畅性，并受ROS，PKC和黄蛋蛋白的影响。