Molecular mechanism of Klotho gene in the mitochondrial bioenergetics during aging system

Klotho基因在衰老系统线粒体生物能学中的分子机制

基本信息

批准号：
22591142
负责人：
KOGA Yasutoshi
金额：
$ 2.91万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

Premature aging model (klotho, kl-/-) and natural aged (CD-1) mice were used to compare the mitochondrial energy metabolism and morphometrical property in kidney and brain. Natural aged mice tended to renal hypertrophy with decreasing glomerulus and decreased the total protein content, oxygen consumption and respiratory chain enzyme activities, complex I, II, I-III, II-III, and IV, in renal mitochondria. Klotho mice had contracted kidney with decreasing normal glomerulus and decreased oxygen consumption with increasing the total protein content, however the most respiratory chain enzyme activities retained in renal mitochondria. Klotho mice reduced only complex II and I-III activities. In endbrain, Natural aged mice had hypertrophic mitochondria with numerical decreasing and tend to decrease oxygen consumptions and respiratory chain enzyme activities in synaptosome and synaptosomal mitochondria. Klotho mice had atrophy of the cerebrum with abnormal distribution of neuronal cellsin cerebral cortex layers, mortar region, and with atrophic mitochondria. Klotho mice preserved the oxygen consumptions and the respiratory chain enzyme activities, only reducing complex II activity, with increasingtotal protein contents in synaptosome and synaptosomal mitochondria. Klotho mouse defected klotho gene expression causes the mitochondrial dysfunction in kidney and brain to change some morphological properties with similarities to natural aging mouse. However, the dysfunction and the morphometrical properties make some differences with the natural aging mice. It is indicated that klotho mouse induce mitochondrial dysfunction by abnormal proteins accumulation affected to neuronalmigration that cerebral growth retardation occur for premature aging model.

使用过早衰老模型（klotho，kl-/-）和自然衰老（CD-1）小鼠来比较肾脏和大脑中的线粒体能量代谢和形态特征。自然衰老的小鼠肾趋于肥大，肾小球减少，肾线粒体中总蛋白含量、耗氧量和呼吸链酶活性、复合物I、II、I-III、II-III和IV降低。 Klotho小鼠的肾脏收缩，正常肾小球减少，耗氧量增加，总蛋白含量增加，但大部分呼吸链酶活性保留在肾线粒体中。 Klotho 小鼠仅降低复合物 II 和 I-III 活性。自然衰老小鼠脑内线粒体肥大，数量减少，突触体和突触体线粒体耗氧量和呼吸链酶活性趋于降低。 Klotho小鼠大脑萎缩，大脑皮层、臼齿区神经元细胞分布异常，线粒体萎缩。 Klotho小鼠保留了耗氧量和呼吸链酶活性，仅降低了复合体II活性，突触体和突触体线粒体中的总蛋白含量增加。 Klotho 小鼠的 klotho 基因表达缺陷会导致肾脏和大脑的线粒体功能障碍，从而改变一些形态特性，与自然衰老的小鼠相似。然而，功能障碍和形态特征与自然衰老小鼠存在一些差异。表明klotho小鼠通过影响神经元迁移的异常蛋白质积累诱导线粒体功能障碍，导致早衰模型出现脑生长迟缓。