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.

过早衰老模型（Klotho，KL - / - ）和天然老化（CD-1）小鼠用于比较肾脏和大脑中的线粒体能量代谢和形态学特性。天然老年小鼠随着肾小球的降低而趋于肾脏肥大，并减少蛋白质含量，氧气消耗和呼吸链酶活性，复合物I，II，I-III，II-IIII，II-III和IV，在肾脏线粒体中。 Klotho小鼠因肾小球正常的肾小球降低并随着总蛋白质含量的增加而降低了肾脏，但是肾脏链酶活性保留在肾脏线粒体中。 Klotho小鼠仅减少了复合体II和I-III活动。在末端脑中，天然老化小鼠的肥厚线粒体具有数值降低，并且倾向于减少氧气消耗量，并在突触体和突触体线粒体中减少氧气和呼吸链酶活性。 klotho小鼠患有大脑的萎缩，具有异常的神经元细胞分布，脑部皮质层，迫击炮区和萎缩性线粒体。 Klotho小鼠保留了氧气消耗和呼吸链酶活性，仅降低了复合物II活性，并在突触体和突触体线粒体中增加了替代蛋白含量。 Klotho小鼠缺陷Klotho基因表达会导致肾脏和大脑中的线粒体功能障碍改变与自然衰老小鼠相似的形态学特性。但是，功能障碍和形态图的特性与天然老化小鼠有所不同。据表明，klotho小鼠会诱导对神经元迁移影响的异常蛋白的积累诱导线粒体功能障碍，即过早衰老模型发生大脑生长迟缓。