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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.

采用早衰模型(Klotho，KL-/-)和自然衰老小鼠(CD-1)比较肾和脑线粒体能量代谢和形态计量学特性。自然衰老小鼠肾脏肥大，肾小球减少，肾线粒体总蛋白含量、氧耗量和呼吸链酶活性降低，复合体I、II、I-III、II-III和IV降低。Klotho小鼠肾脏收缩，正常肾小球减少，氧耗量随总蛋白含量增加而减少，但肾线粒体呼吸链酶活性最高。Klotho小鼠只减少了复合体II和I-III的活性。在终脑中，自然衰老小鼠线粒体肥大，数量减少，并有降低突触体和突触体线粒体耗氧量和呼吸链酶活性的趋势。Klotho小鼠大脑萎缩，大脑皮质各层、砂膜区神经细胞分布异常，线粒体萎缩。Klotho小鼠维持耗氧量和呼吸链酶活性，仅降低复合体II活性，增加突触体和突触体线粒体总蛋白含量。Klotho小鼠Klotho基因缺陷表达导致肾脏和脑内线粒体功能障碍改变一些与自然衰老小鼠相似的形态特征。然而，功能障碍和形态计量学特性与自然衰老的小鼠有所不同。提示Klotho小鼠通过影响神经元迁移的蛋白质异常堆积导致线粒体功能障碍，导致脑发育迟缓。