Phosphorylation of histone H2AX in the mouse brain from development to senescence.
Phosphorylation of histone H2AX in the mouse brain from development to senescence.
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DOI：
10.3390/ijms15011554
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发表时间：
2014-01-21
影响因子：
5.6
通讯作者：
Merighi A
中科院分区：
文献类型：
--
作者：
Barral S;Beltramo R;Salio C;Aimar P;Lossi L;Merighi A
组蛋白H2 AX（γ H2 AX形式）的磷酸化是对DNA损伤的早期反应，也是神经系统外几种细胞和组织中衰老和疾病的标志物。关于神经元中H2 AX的体内磷酸化知之甚少，尽管有人认为γ H2 AX是神经元危害的早期标志物，从而打开了靶向其作为神经保护策略的可能性。用5-溴-2-脱氧尿苷（BrdU）标记DNA合成细胞后，用光镜、电镜免疫细胞化学和Western blotting技术研究了γ H2 AX在发育期、出生后、成年和衰老期（2岁）小鼠脑内的分布。在运动间核、有丝分裂染色体和凋亡核中出现局灶性和/或弥漫性γ H2 AX免疫染色。免疫反应性主要与神经发生区域相关，即，端脑的脑室下区（SVZ）、小脑皮质，以及海马齿状回的颗粒下区（尽管程度要小得多）。此外，γ H2 AX在成年和衰老的大脑皮质中高度表达，特别是梨状皮质。双标记实验表明，神经发生脑区的γ H2 AX在时间和功能上与神经元前体细胞的增殖和凋亡相关，即，C型转运放大细胞（SVZ）和颗粒细胞前体（小脑）。相反，掺入S期标记BrdU的γ H2 AX免疫反应性皮质神经元不表达增殖标记磷酸化组蛋白H3，表明这些有丝分裂后细胞经历显著的DNA损伤反应。我们的研究为更好地理解H2 AX磷酸化在正常大脑中的作用铺平了道路，并为设计保护中枢神经系统（CNS）退行性疾病中神经元前体和成熟神经元的新策略提供了额外的数据。
Phosphorylation of the histone H2AX (γH2AX form) is an early response to DNA damage and a marker of aging and disease in several cells and tissues outside the nervous system. Little is known about in vivo phosphorylation of H2AX in neurons, although it was suggested that γH2AX is an early marker of neuronal endangerment thus opening the possibility to target it as a neuroprotective strategy. After experimental labeling of DNA-synthesizing cells with 5-bromo-2-deoxyuridine (BrdU), we studied the brain occurrence of γH2AX in developing, postnatal, adult and senescent (2 years) mice by light and electron microscopic immunocytochemistry and Western blotting. Focal and/or diffuse γH2AX immunostaining appears in interkinetic nuclei, mitotic chromosomes, and apoptotic nuclei. Immunoreactivity is mainly associated with neurogenetic areas, i.e., the subventricular zone (SVZ) of telencephalon, the cerebellar cortex, and, albeit to a much lesser extent, the subgranular zone of the hippocampal dentate gyrus. In addition, γH2AX is highly expressed in the adult and senescent cerebral cortex, particularly the piriform cortex. Double labeling experiments demonstrate that γH2AX in neurogenetic brain areas is temporally and functionally related to proliferation and apoptosis of neuronal precursors, i.e., the type C transit amplifying cells (SVZ) and the granule cell precursors (cerebellum). Conversely, γH2AX-immunoreactive cortical neurons incorporating the S phase-label BrdU do not express the proliferation marker phosphorylated histone H3, indicating that these postmitotic cells undergo a significant DNA damage response. Our study paves the way for a better comprehension of the role of H2AX phosphorylation in the normal brain, and offers additional data to design novel strategies for the protection of neuronal precursors and mature neurons in central nervous system (CNS) degenerative diseases.
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影响因子：
5.1
作者：
Jeon GS;Kim KY;Hwang YJ;Jung MK;An S;Ouchi M;Ouchi T;Kowall N;Lee J;Ryu H
通讯作者：
Ryu H
影响因子：
1.6
作者：
Dickey JS;Redon CE;Nakamura AJ;Baird BJ;Sedelnikova OA;Bonner WM
通讯作者：
Bonner WM
影响因子：
3.4
作者：
Nowak, E;Etienne, O;Boussin, FD
通讯作者：
Boussin, FD
影响因子：
5.3
作者：
Maslov, AY;Barone, TA;Pruitt, SC
通讯作者：
Pruitt, SC
影响因子：
--
作者：
Myung, Na-Hye;Zhu, Xiongwei;Lee, Hyoung-gon
通讯作者：
Lee, Hyoung-gon