REGULATION OF ENERGY METABOLISM IN AGING AND DISEASE--CARDIOVASCULAR SYSTEM

这个项目研究了线粒体在老年和老年中的功能。 一种病理状态，在这种状态下能量转导减少 线粒体可能会影响组织的存活。我们今年的重点是 糖尿病大鼠心脏线粒体功能的研究 链脲佐菌素治疗慢性粒细胞白血病的临床研究 疾病(治疗后6-8周)。我们已经延长了去年的 相对不能提高线粒体内游离的研究结果 糖尿病大鼠心肌细胞内钙离子浓度的变化 电刺激。这是使用INDO 1：AM-Load和 Mn2+-荧光猝灭单个心肌细胞 显微镜。在升高的过融合液存在时的刺激(4赫兹) Ca~(2+)浓度(3.5 mM)使[Ca~(2+)]_m明显变小 在糖尿病动物的心肌细胞中，当与对照组相比。 从两组动物中分离出心肌线粒体 然而，在钙吸收或释放的动力学上没有差异 使用金色指示剂进行了研究。由此得出结论： 糖尿病动物细胞内[Ca~(2+)]_m未能升高， 其大小将被预期通过以下方式限制激活 丙酮酸脱氢酶的钙离子和三羧酸循环，源于 该模型中的激发-收缩耦合失效。

This project examines mitochondrial functioning in old age and in pathological states in which decreased energy transduction by mitochondria may compromise tissue survival. We have focused this year on mitochondrial functioning in the hearts of rats made diabetic by treatment with streptozotocin and studied in the chronic stage of the disease (6-8 weeks after treatment). We have extended last year's findings on the relative inability to elevate intramitochondrial free Ca2+ ([Ca2+]m) of cardiac myocytes from diabetic rats, when subjected to electrical stimulation. This was studied using indo 1:AM-loaded and Mn2+- quenched individual cardiac myocytes, using fluorescence microscopy. Stimulation (4 Hz) in the presence of elevated superfusate Ca2+ concentration (3.5mM) gave significantly smaller values of [Ca2+]m in myocytes from diabetic animals, when compared with controls. Isolation of cardiac mitochondria from the two groups of animals revealed no differences in the kinetics of Ca2+ uptake or release, however, when studied using metallochromic indicators. It is concluded that the failure to elevate [Ca2+]m in cells from the diabetic animals, which is of a magnitude such that it would be expected to limit the activation by Ca2+ of pyruvate dehydrogenase and the tricarboxylate cycle, derives from a failure of excitation-contraction coupling in this model.