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p53 和时钟基因在由于长期的紫外线 A 眼照射而导致的记忆和学习能力下降中发挥重要作用。

p53 and clock genes play an important role in memory and learning ability depression due to long-term ultraviolet A eye irradiation.

机构信息

Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.

出版信息

Photochem Photobiol Sci. 2021 May;20(5):677-685. doi: 10.1007/s43630-021-00055-5. Epub 2021 May 19.

DOI:10.1007/s43630-021-00055-5
PMID:34009633
Abstract

BACKGROUND

Long-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear.

OBJECTIVES

In this study, ICR mice were used to study the effects of long-term UVA eye irradiation.

METHODS

The eyes of mice were exposed to UVA from an FL20SBLB-A lamp three times a week for 1 year. Then, we analyzed memory and learning ability in the mice using water maze and step-through passive avoidance tests, and measured the levels of p53, Period2 (Per2), Clock, brain and muscle Arnt-like protein-1 (Bmal1), nicotinamide mononucleotide adenylyltransferase (NMNAT) activity, nicotinamide phosphoribosyltransferase (NAMPT) activity, nicotinamide adenine dinucleotide (NAD), and sirtuin 1 (Sirt1) in the brains of treated and control animals.

RESULTS

The results showed that the p53 level increased significantly following long-term UVA eye irradiation, whereas the levels of Period2, Bmal1, Clock, NMNAT and NAMPT activities, NAD, and Sirt1 decreased significantly. Furthermore, we found that p53 inhibition ameliorated the UVA eye irradiation-induced depression of memory and learning ability.

CONCLUSION

These results indicate that long-term UVA eye irradiation stimulates p53, inhibits the clock gene, and reduces Sirt1 production in the NAD constructional system, resulting in reduced memory and learning ability.

摘要

背景

长期的紫外线 A(UVA)眼部照射会降低小鼠的记忆和学习能力。然而,其潜在机制尚不清楚。

目的

本研究使用 ICR 小鼠来研究长期 UVA 眼部照射的影响。

方法

每周三次用 FL20SBLB-A 灯对小鼠的眼睛进行 UVA 照射,持续 1 年。然后,我们使用水迷宫和穿梭式被动回避测试分析小鼠的记忆和学习能力,并测量 p53、Period2(Per2)、Clock、脑和肌肉芳香烃受体核转录因子样蛋白 1(Bmal1)、烟酰胺单核苷酸腺苷酰转移酶(NMNAT)活性、烟酰胺磷酸核糖转移酶(NAMPT)活性、烟酰胺腺嘌呤二核苷酸(NAD)和沉默调节蛋白 1(Sirt1)在处理组和对照组动物大脑中的水平。

结果

结果表明,长期 UVA 眼部照射后 p53 水平显著升高,而 Per2、Bmal1、Clock、NMNAT 和 NAMPT 活性、NAD 和 Sirt1 水平显著降低。此外,我们发现 p53 抑制可改善 UVA 眼部照射引起的记忆和学习能力下降。

结论

这些结果表明,长期的 UVA 眼部照射刺激 p53,抑制时钟基因,并减少 NAD 构建系统中的 Sirt1 产生,导致记忆和学习能力下降。

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Evidence that transcriptional activation by p53 plays a direct role in the induction of cellular senescence.有证据表明,p53介导的转录激活在细胞衰老的诱导过程中起直接作用。
Oncogene. 1996 Nov 21;13(10):2097-104.
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