Activation of cell death pathways in the inner ear of the aging CBA/J mouse.
Activation of cell death pathways in the inner ear of the aging CBA/J mouse.
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DOI：
10.1016/j.heares.2009.04.019
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发表时间：
2009-08
期刊：
影响因子：
2.8
通讯作者：
Schacht, Jochen
中科院分区：
文献类型：
--
作者：
Sha, Su-Hua;Chen, Fu-Quan;Schacht, Jochen
我们先前已经证明，氧化应激在衰老的CBA/J小鼠的内耳中增加，并可能导致感觉系统功能的丧失。我们现在研究这些动物耳蜗中细胞死亡通路的激活。中年(12个月)和老年(18-26个月)听力障碍的小鼠表现出外毛细胞核的凋亡和较小程度的坏死特征。与年轻(3个月)的动物相比，老化的耳蜗中的内源性和外源性细胞死亡通路都被蛋白质的易位或翻译后修饰激活。胞浆细胞色素C增加，与caspase9形成络合物，并激活caspase9。核酸内切酶G移位到衰老的外毛细胞的细胞核，提示其作为一种凋亡的DNA酶的功能。在中年而不是老年的动物中，被切割的(因此也是活跃的)形式的钙蛋白酶I和钙蛋白酶II增加，而活性组织蛋白酶D一过性升高。最后，p38MAPK和JNK的磷酸化增加暗示了MAPK通路的额外参与。结果表明，衰老小鼠听觉器官的毛细胞激活了多种细胞死亡途径，所有这些途径都可能与氧化应激有关。
We have previously demonstrated that oxidative stress increases in the inner ear of aging CBA/J mice and might contribute to the loss of function of the sensory system. We now investigate the activation of cell death pathways in the cochlea of these animals. Middle-aged (12 months) and old (18-26 months) mice with hearing deficits displayed outer hair cell nuclei with apoptotic and, to a lesser extent, necrotic features. Both intrinsic and extrinsic cell death pathways were activated by translocation or post-translational modification of proteins in the aging cochlea as compared to young (3 months) animals. Cytosolic cytochrome C increased, formed a complex with, and activated caspase 9. Endonuclease G translocated to the nuclei of aging outer hair cells suggesting its function as an apoptotic DNase. The cleaved (and hence active) forms of calpain I and calpain II increased while active cathepsin D was transiently elevated in middle-aged but not old animals. Finally, increases in the phosphorylation of p38 MAPK and JNK implicated the additional involvement of the MAPK pathway. The results suggest that multiple cell death pathways, all potentially linked to oxidative stress, are activated in hair cells of the auditory organ in aging mice.
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影响因子：
2.8
作者：
Hu, BH;Henderson, D;Nicotera, TM
通讯作者：
Nicotera, TM
影响因子：
4.8
作者：
Ishihara, Y;Shimamoto, N
通讯作者：
Shimamoto, N
影响因子：
16.2
作者：
Deshmukh, M;Johnson, EM
通讯作者：
Johnson, EM
DOI：
10.1002/neu.20054
发表时间：
2004-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Matsui, JI;Gale, JE;Warchol, ME
通讯作者：
Warchol, ME
影响因子：
64.5
作者：
Liu, ZG;Hsu, HL;Karin, M
通讯作者：
Karin, M