Pax6影响小鼠衰老大脑中Ras-Raf-ERK1/2。

IF 4.1 4区 医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2023-12-01 Epub Date: 2023-07-12 DOI:10.1007/s10522-023-10044-z
Khushboo Srivastava, Rajnikant Mishra
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引用次数: 0

摘要

Pax6是一种转录因子和多功能蛋白,在衰老过程中发生变化。它还与参与细胞代谢和生存信号通路的调节蛋白相互作用,包括Ras-GAP。Ras、Raf和ERK1/2的许多形式是已知的,但在衰老过程中,大脑无法获得关于其区域特异性表达模式的信息。因此,本研究旨在评估海马、尾状核、杏仁核、大脑皮层、小脑和嗅叶中Pax6的表达以及Ras、Raf、ERK1/2的形式。在神经胶质细胞系的共培养(PC-12,C6胶质细胞,U-87MG)中评估Pax6与Ras、Raf和ERK1/2的相关性。通过siRNA介导的敲除和表达模式Ras-Raf-Erk1/2来评估Pax6的影响。通过RT-PCR和荧光素酶报告基因测定分析了Pax6的活性以及5’AMP、野生型和突变体ERK的影响。结果表明,年轻和老年小鼠大脑不同区域的Pax6、Ras、Raf、ERK1/2的变化与年龄有关。Erk1/2对Pax6表现出协同活性。
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Pax6 affects Ras-Raf-ERK1/2 in mouse aging brain.

Pax6, a transcription factor and multifunctional protein, changes during aging. It also interacts with regulator proteins involved in cell metabolism and survival signalling pathways including Ras-GAP. Many forms of Ras, Raf and ERK1/2 are known but information on their region-specific expression patterns are unavailable from brain during aging. Therefore, it has been intended to evaluate expressions of Pax6 and forms of Ras, Raf, ERK1/2 in hippocampus, caudate nucleus, amygdale, cerebral cortex, cerebellum and olfactory lobe. Association of Pax6 with Ras, Raf and ERK1/2 was evaluated in co-culture (PC-12, C6-glia, U-87 MG) of neuroglia cell lines. Impacts of Pax6 were evaluated by siRNA mediated knockdown and expression patterns Ras-Raf-Erk1/2. Analysis of activities of Pax6 and impacts of 5'AMP, wild-type and mutant ERK were done by RT-PCR and luciferase reporter assay. Results indicate age-dependent changes of Pax6, Ras, Raf, ERK1/2 in different regions of brain of young and old mice. Erk1/2 shows synergistic activities to Pax6.

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来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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