权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

STRESS PROTEIN 60 DURING MYOCARDIAL ISCHEMIA

心肌缺血期间的应激蛋白 60

基本信息

批准号：
2211222
负责人：
RUBEN MESTRIL
金额：
$ 10.66万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1998-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2211222
关键词：
DNA repair antisense nucleic acid gene expression genetic promoter element genetically modified animals heart cell laboratory mouse laboratory rat messenger RNA mitochondria molecular cloning muscle cells myocardial ischemia /hypoxia oxidative stress stress proteins transfection /expression vector

项目摘要

Coronary artery disease can lead to chronic heart failure, need for revascularization (by-pass surgery), or life-threatening cardiac arrhythmias. It is the cause of one and a half million acute myocardial infarctions per year in the USA, more than half of them lethal. Its cost is the highest of all Current medical diseases in the nation. Coronary artery disease affects the blood supply of the heart muscle (myocardium) and, therefore, decreases oxygen delivery to myocardial cells. The mitochondria of cardiac myocytes is one of the major targets for ischemia- induced damage. Limitations of oxygen delivery reduces mitochondrial oxidative phosphorylation and contributes to the reduction of intracellular ATP levels. Some investigators have indicated that the inability of the mitochondria to self-repair following restoration of blood flow may be one of the crucial events leading to the ultimate death of myocardial cells. Although it is not clear if sarcolemmal or mitochondrial damage is the main event in the irreversible damage of the myocardial cell, the role of mitochondrial changes in decreased myocardial functions are not questioned. Recent studies have shown that heat shock protein (HSP) 60, which is a member of the stress protein family and are thought to have a protective role during oxidative stress, is required for the assembly of multimeric enzyme complexes within the mitochondria. We have recently found that during acute occlusion of the descending coronary artery for 30 minutes in the rat heart, which leads to ischemia in the left ventricle, there is a marked and specific increase in HSP6O mRNA level. This finding leads us to believe that HSP6O as other related HSPs may have a protective role and is probably involved in the repair of the mitochondrial enzymatic complexes vital for the normal function of the mitochondria. It is our objective to investigate this ischemia-induced change in HSP6O expression and determine if HSP60 mediates protection processes in the mitochondria that contribute to recovery from ischemic injury in the myocardial cell.

冠状动脉疾病可导致慢性心力衰竭，需要血运重建(旁路手术)或危及生命的心脏心律不齐。它是150万急性心肌梗死的原因在美国，每年有超过一半的脑梗塞是致命的。它的成本是美国目前所有医学疾病中最高的。冠状动脉动脉疾病影响心肌(心肌)的血液供应因此，减少了对心肌细胞的氧气输送。这个心肌细胞线粒体是心肌缺血的主要靶点之一。诱导性损害。氧输送的限制减少了线粒体氧化磷酸化，有助于减少细胞内三磷酸腺苷水平。一些调查人员表示，线粒体在修复后不能自我修复血液流动可能是导致最终死亡的关键事件之一心肌细胞。尽管目前还不清楚肌膜或线粒体损伤是心肌细胞不可逆性损伤的主要事件。心肌细胞线粒体改变在心肌细胞减少中的作用功能不会受到质疑。最近的研究表明，热休克蛋白(HSP)60，是应激蛋白家族的成员，是被认为在氧化应激过程中具有保护作用，是线粒体内多聚体酶复合体的组装。我们最近发现，在急性冠状动脉降支闭塞期间在大鼠心脏中动脉注射30分钟，导致心脏缺血左心室HSP60mRNA有明显的、特异性的增加水平。这一发现使我们相信HSP60和其他相关的HSP一样可能起到保护作用，并可能参与修复线粒体酶复合体对细胞的正常功能至关重要线粒体。我们的目标是研究这种由缺血引起的热休克蛋白60表达的变化及热休克蛋白60是否参与保护线粒体中有助于脑缺血恢复的过程心肌细胞的损伤。