脑衰老过程中c-Jun氨基末端激酶的激活及线粒体丙酮酸脱氢酶活性的下降
Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging.
作者信息
Zhou Qiongqiong, Lam Philip Y, Han Derick, Cadenas Enrique
机构信息
Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205-2186, USA.
出版信息
FEBS Lett. 2009 Apr 2;583(7):1132-40. doi: 10.1016/j.febslet.2009.02.043. Epub 2009 Mar 9.
Abstract
Mitochondrial dysfunction is often associated with aging and neurodegeneration. c-Jun-N-terminal kinase (JNK) phosphorylation and its translocation to mitochondria increased as a function of age in rat brain. This was associated with a decrease of pyruvate dehydrogenase (PDH) activity upon phosphorylation of the E(1alpha) subunit of PDH. Phosphorylation of PDH is likely mediated by PDH kinase, the protein levels and activity of which increased with age. ATP levels were diminished, whereas lactic acid levels increased, thus indicating a shift toward anaerobic glycolysis. The energy transduction deficit due to impairment of PDH activity during aging may be associated with JNK signaling.
摘要
线粒体功能障碍常与衰老和神经退行性变相关。在大鼠脑中，c-Jun氨基末端激酶（JNK）的磷酸化及其向线粒体的转位随年龄增长而增加。这与丙酮酸脱氢酶（PDH）E（1α）亚基磷酸化后PDH活性降低有关。PDH的磷酸化可能由PDH激酶介导，其蛋白水平和活性随年龄增长而增加。ATP水平降低，而乳酸水平升高，这表明代谢向无氧糖酵解转变。衰老过程中由于PDH活性受损导致的能量转导缺陷可能与JNK信号传导有关。
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