The role of p38 in mitochondrial respiration in male and female mice.
The role of p38 in mitochondrial respiration in male and female mice.
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DOI：
10.1016/j.neulet.2013.04.004
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发表时间：
2013-06-07
影响因子：
2.5
通讯作者：
Jung M
中科院分区：
文献类型：
--
作者：
Ju X;Wen Y;Metzger D;Jung M
p38是一种促分裂原活化蛋白激酶，介导细胞生长、细胞分化和突触可塑性。本研究的目的是确定在正常条件下，p38在维持雄性和雌性小鼠线粒体呼吸中发挥作用的程度。为了实现这一目标，我们已经产生了转基因小鼠，缺乏p38小脑浦肯野神经元交叉Pcp2（浦肯野细胞蛋白2）-Cre小鼠与p38loxP/loxP小鼠。然后从转基因和野生型小鼠分离小脑线粒体，使用XF 24呼吸计测量线粒体呼吸。用RT-PCR和免疫印迹法检测小脑细胞色素c氧化酶（考克斯）mRNA和蛋白的表达。另外，使用HT 22细胞来确定17 β-雌二醇（E2）和考克斯在线粒体呼吸中的参与。浦肯野神经元中p38基因敲除仅抑制雄性小鼠的线粒体呼吸，仅增加雌性小鼠的考克斯表达。叠氮化钠（SA）抑制考克斯可显著抑制HT 22细胞线粒体呼吸，并受到E2的保护。这些数据表明，p38是雄性小鼠线粒体呼吸所必需的。当p38低于正常水平时，雌性可通过考克斯上调来维持线粒体呼吸。
p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38loxP/loxP mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation.
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影响因子：
4.2
作者：
Jung ME;Ju X;Metzger DB;Simpkins JW
通讯作者：
Simpkins JW
影响因子：
4.2
作者：
Jung ME;Ju X;Simpkins JW;Metzger DB;Yan LJ;Wen Y
通讯作者：
Wen Y
DOI：
10.1073/pnas.0903563106
发表时间：
2009-08-25
影响因子：
11.1
作者：
Yao, Jia;Irwin, Ronald W.;Brinton, Roberta Diaz
通讯作者：
Brinton, Roberta Diaz
影响因子：
5
作者：
Hsieh, Ya-Ching;Yu, Huang-Ping;Chaudry, Irshad H.
通讯作者：
Chaudry, Irshad H.
影响因子：
3.7
作者：
Kitamura N;Nakamura Y;Miyamoto Y;Miyamoto T;Kabu K;Yoshida M;Futamura M;Ichinose S;Arakawa H
通讯作者：
Arakawa H