Kilgore J L, Musch T I, Ross C R
Department of Kinesiology, Kansas State University Manhattan 66506, USA.
Basic Res Cardiol. 1996 Jul-Aug;91(4):283-8. doi: 10.1007/BF00789300.
Hypoxia and altered hemodynamic status, both components of myocardial infarction, have been shown to be potent inducers of the 70 kD family of heat shock proteins (HSP70). We hypothesized that after infarction, the surviving myocardium would synthesize HSP70 proteins in a temporally and regionally distinct pattern. We believed that there would be a lack of an HSP70 response in the infarcted area (I), reflecting the loss of viable cells. We further postulated that tissues bordering infarctions (M) would have a compromised HSP70 response. Conversely, we proposed that HSP70 would be induced in septal tissues (S) of the infarcted heart, as a hypertrophic adaptation. A rat model of myocardial infarction was used to examine the changes in relative concentration and distribution of three major HSP70 family proteins; cytoplasmic HSP72, mitochondrial HSP75, and endoplasmic reticular GRP78 (glucose regulated protein) during 21 days of recovery. While all three HSP70 family proteins investigated were detected in all hearts from all groups at all time periods, experimental treatment (infarction) induced changes in relative protein concentrations that varied with time and sample site location. Relative concentrations of HSP72 and GRP78 were unchanged in the 24 h following infarction while relative HSP75 concentrations were halved in M tissues during the same time period. Between days 5 and 7, several changes were noted. M samples displayed nearly twice the relative concentrations of HSP75 and GRP78 after infarction, but showed no change in HSP72. S tissues showed two-fold or larger increases in all three HSP70 family proteins. I samples showed unanticipated increases in HSP75 and GRP78 during this time period. After 14 to 21 days of recovery, HSP70 family protein concentration levels in M, S, and I tissues from infarcted hearts had returned to levels similar to those seen in control animals. We conclude that the myocardium is unable to, or does not, mount an immediate HSP70 response after infarction but does recover such activity by 5-7 days after infarction.
缺氧和血流动力学状态改变是心肌梗死的两个组成部分，已被证明是热休克蛋白70kD家族（HSP70）的强效诱导剂。我们假设，梗死后，存活的心肌会以时间和区域上不同的模式合成HSP70蛋白。我们认为梗死区域（I）缺乏HSP70反应，这反映了活细胞的丧失。我们进一步推测，梗死周边组织（M）的HSP70反应会受损。相反，我们提出梗死心脏的间隔组织（S）会诱导HSP70，作为一种肥厚性适应。使用大鼠心肌梗死模型来检查在恢复的21天内三种主要HSP70家族蛋白；细胞质HSP72、线粒体HSP75和内质网GRP78（葡萄糖调节蛋白）的相对浓度和分布变化。虽然在所有时间段所有组的所有心脏中都检测到了所研究的所有三种HSP70家族蛋白，但实验处理（梗死）诱导了相对蛋白浓度的变化，这些变化随时间和样本位点位置而变化。梗死24小时内HSP72和GRP78的相对浓度没有变化，而同一时间段内M组织中HSP75的相对浓度减半。在第5天到第7天之间，观察到了一些变化。梗死M样本显示HSP75和GRP78的相对浓度几乎是梗死前的两倍，但HSP72没有变化。S组织中所有三种HSP70家族蛋白增加了两倍或更多。在此时间段内，I样本中HSP75和GRP78出现了意外增加。恢复14至21天后，梗死心脏的M、S和I组织中HSP70家族蛋白浓度水平已恢复到与对照动物相似的水平。我们得出结论，心肌梗死后无法或不会立即产生HSP70反应，但在梗死后5 - 7天会恢复这种活性。
