SIRT1去乙酰化修饰p53抑制IL-1β介导的软骨终板细胞衰老

周年; 胡侦明; 林鑫; 郝杰

doi:10.16016/j.1000-5404.201806002

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SIRT1去乙酰化修饰p53抑制IL-1β介导的软骨终板细胞衰老

基础医学 | 更新时间：2026-01-09

- SIRT1去乙酰化修饰p53抑制IL-1β介导的软骨终板细胞衰老
- SIRT1 inhibits interleukin-1β-mediated cartilage end plate cell senescence via p53 deacetylation
- 第三军医大学学报 2018年40卷第22期页码：2040-2046
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院骨科
- 作者简介：
  
  [ 胡侦明，E-mail: spinecenter@163.com HU Zhenming, E-mail: spinecenter@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81372003);重庆医科大学附属第一医院护理科研基金(HLJJ2016-21);重庆医科大学附属第一医院院内培育基金项目(2017PYJJ-06)
- DOI：10.16016/j.1000-5404.201806002
  中图分类号： R322.71;R329.28;R394.3
- 收稿：2018-06-04，
  
  修回：2018-07-15，
  
  纸质出版：2018-11-30
- 稿件说明：
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周年, 胡侦明, 林鑫, 等. SIRT1去乙酰化修饰p53抑制IL-1β介导的软骨终板细胞衰老[J]. 第三军医大学学报, 2018,40(22):2040-2046.

Nian ZHOU, Zhenming HU, Xin LIN, et al. SIRT1 inhibits interleukin-1β-mediated cartilage end plate cell senescence via p53 deacetylation[J]. Journal of Third Military Medical University, 2018, 40(22): 2040-2046.
周年, 胡侦明, 林鑫, 等. SIRT1去乙酰化修饰p53抑制IL-1β介导的软骨终板细胞衰老[J]. 第三军医大学学报, 2018,40(22):2040-2046. DOI： 10.16016/j.1000-5404.201806002.

Nian ZHOU, Zhenming HU, Xin LIN, et al. SIRT1 inhibits interleukin-1β-mediated cartilage end plate cell senescence via p53 deacetylation[J]. Journal of Third Military Medical University, 2018, 40(22): 2040-2046. DOI： 10.16016/j.1000-5404.201806002.

摘要

目的

探讨沉默信息调节因子2同源蛋白1(silent information regulation 2 homolog-1，SIRT1)对软骨终板细胞衰老的调控作用及相关机制。

方法

IL-1β处理软骨终板细胞，通过细胞周期检测、衰老相关β-半乳糖苷酶染色、衰老相关通路激活情况，判断IL-1β对软骨终板细胞衰老的影响；调控SIRT1的表达或活性后，通过上述方法明确SIRT1对IL-1β介导软骨终板细胞衰老具有调控作用，并通过抑制相关通路活性，进一步探讨SIRT1调控软骨终板细胞衰老的机制。

结果

IL-1β处理软骨终板细胞后G

期细胞比例明显增加(

0.05)，衰老相关β-半乳糖苷酶染色阳性率升高(

0.05)，衰老相关通路p53-p21中p53、p21 mRNA表达水平明显增加(

0.05)；增加SIRT1的表达后p53蛋白乙酰化水平明显降低(

0.05)，p21蛋白表达明显降低(

0.05)，G

期细胞比例较对照组明显较少(

0.05)，β-半乳糖苷酶染色阳性率明显降低(

0.05)，而尼克酰胺抑制SIRT1活性后p53蛋白乙酰化水平升高(

0.05)，p21蛋白表达增加(

0.05)，G

期细胞比例较对照组明显增加(

0.05)，β-半乳糖苷酶染色阳性率明显增高(

0.05)。无论使用尼克酰胺抑制SIRT1激活p53-p21通路与否，在使用p53抑制剂PFT-α后，p21的表达、G

期细胞比例、β-半乳糖苷酶染色阳性率均无明显变化(

0.05)。

结论

IL-1β介导了软骨终板细胞的衰老，SIRT1能够通过去乙酰化修饰p53抑制IL-1β介导的软骨终板细胞的衰老。

Abstract

Objective

To investigate the regulatory role of silent information regulation 2 homolog-1 (SIRT1) in interleukin-1β (IL-1β)-mediated cartilage end plate (CEP) cell senescence and explore the mechanism.

Methods

CEP cells were isolated from resected lumbar intervertebral disc tissues from a patient with degenerative lumbar disc disease. The cultured cells were treated with IL-1β and examined for changes in cell cycle

senescence associated β-galactosidase (SA-β-Gal) and expression levels of senescence-related signal pathway genes to assess IL-1β-induced cell senescence. The CEP cells were infected with the recombinant adenoviral vector Ad-SIRT1 to induce SIRT1 over-expression or treated with nicotinamide for inhibiting SIRT1 activity

and changes in the cell cycle

SA-β-Gal and expression levels of senescence-related signal pathway genes were observed in response to IL-1 treatment.

Results

In cultured CEP cells

IL-1β significantly increased the percentages of G

phase cells (

0.05) and SA-β-Gal-positive cells (

0.05) and enhanced the mRNA levels of p53 and p21 (

0.05). SIRT1 overexpression significantly lowered the levels of acetylated p53 and the protein expression of p21 (

0.05)

and decreased the percentages of G1 phase cells (

0.05) and SA-β-Gal-positive cells (

0.05) in IL-1β-treated cells. Treatment of the cells with nicotinamide significantly enhanced the levels of acetylated p53 and the protein expression of p21 (

0.05) and increased the percentages of G

phase cells (

0.05) and SA-β-Gal-positive cells (

0.05). PTF-α significantly inhibited p21 protein expression and decreased the percentages of G

phase cells (

0.05) and SA-β-Gal-positive cells (

0.05) irrespective of nicotinamide treatment.

Conclusion

IL-1β can mediate CEP cell senescence

which can be inhibited by SIRT1

via

p53 deacetylation.

关键词

Keywords

references

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