REGULATION OF ENERGY METABOLISM IN AGING AND DISEASE

该项目研究了老年人和老年人的线粒体功能， 线粒体能量传导减少的病理状态 可能危及组织存活。 今年的实验结果来自于 与心力衰竭和心肌细胞死亡有关的两个范例。 （一） 我们研究了心脏收缩性能和线粒体代谢 两个仓鼠品系（B10 14.6和TO-2）作为模型， 基因决定的扩张型心肌病，以及健康对照 动物 来自B10 14.6和TO-2动物的心脏发育较少 健康的心脏，如前所述。 另外还有按 活性中存在较小部分的丙酮酸脱氢酶， 在B10 14.6（45%）和TO-2（20%）动物中的去磷酸化形式（PDH A）， 与对照组（86%）相比，当底物为葡萄糖时。 的 结果表明丙酮酸脱氢酶的比率稳定变化 两种心肌病菌株中激酶：磷酸酶活性： 此外，α-酮戊二酸脱氢酶显著降低， 并因此在TO-2动物中具有克雷布斯循环氧化的潜力。 (2)我们 也开始了一项关于线粒体能量的研究 转导在缺血性衰竭中的作用，使用大鼠心肌细胞作为模型。 测量罗丹明1、2、3的荧光，作为线粒体的指示。 膜电位（Δ psi）。 用以下物质装载细胞的条件 罗丹明1，2，3已建立与细胞悬浮液：荧光 单细胞显微镜检查应该能够将细胞的变化关联起来， 收缩状态，线粒体游离钙和Δ psi 模拟缺血和再灌注。

This project examines mitochondrial functioning in old age and in pathological states in which decreased energy transduction by mitochondria may compromise tissue survival. Experimental results this year derive from two paradigms relating to heart failure and death of cardiac myocytes. (1) We have studied heart contractile performance and mitochondrial metabolism of two strains (B10 14.6 and TO-2) of hamster which serve as models of genetically-determined dilated cardiomyopathy, as well as healthy control animals. The hearts from the B10 14.6 and TO-2 animals developed less pressure than the healthy hearts, as reported previously. In addition, a smaller fraction of pyruvate dehydrogenase was present in the active, dephosphorylated form (PDH A) in the B10 14.6 (45%) and TO-2 (20%) animals, compared to the controls (86%), when the substrate was glucose. The results suggest stable changes in the ratio of pyruvate dehydrogenase kinase: phosphatase activity in both cardiomyopathic strains: in addition, there is a markedly reduced alpha-ketoglutarate dehydrogenase, and thus potential for Krebs cycle oxidation, in the TO-2 animal. (2) We have also initiated a study into the role of mitochondrial energy transduction in ischemic failure, using rat cardiac myocytes as models. Fluorescence of rhodamine 1,2,3 is measured, as indicative of mitochondrial membrane potential (delta psi). Conditions for loading the cells with rhodamine 1,2,3 have been established with cell suspensions: fluorescence microscopy of single cells should allow correlation of changes in contractile state, mitochondrial free calcium and delta psi during simulated ischemia and reperfusion.