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|本期目录/Table of Contents|

衰老心肌自噬减退的新机制-转录因子EB的关键作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第5期
页码:
497-500
栏目:
基础研究
出版日期:
2015-05-05

文章信息/Info

Title:
New mechanism of age-related myocardial autophagy decline: Key role of transcription factor EB
作者:
张 乐1; 刘 敏1; 马 颖1; 胡建华1; 纪兆乐1; 马 恒2; 李 妍1
(第四军医大学：1.西京医院心血管内科；
2.基础部生理学教研室，陕西 西安 710032)
Author(s):
ZHANG Le1;  LIU Min1;  MA Ying1;  HU Jian-hua1;  JI Zhao-le1;  MA Heng2;  LI Yan1
(1.Department of Cardiology, Xijing Hospital, 2.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
衰老; 心肌损伤; 自噬; 转录因子EB
Keywords:
aging;  cardiac injury;  autophagy;  transcription factor EB
分类号:
R392.3
DOI:
-
文献标识码:
A
摘要:
目的 探讨转录因子EB（TFEB）在衰老心肌自噬减退中的作用。方法 采用老年（22月龄）雄性C57BL/6小鼠为实验对象，以成年（4月龄）雄性C57BL/6小鼠为对照，分析心肌自噬水平、心肌TFEB表达水平。结果 与成年心肌相比，衰老心肌自噬水平显著降低（P<0.05）。衰老心肌中自噬体标志物Atg5、LC3和Beclin-1，溶酶体标志物LAMP1在蛋白和mRNA水平上均出现降低。与成年心肌相比，衰老心肌TFEB蛋白水平显著降低（P<0.05），衰老心肌细胞核内的TFEB水平下降更为显著（P<0.05），提示衰老心肌TFEB转录能力减退。给予小剂量雷帕霉素处理，可提高衰老心肌细胞核内TFEB水平，并且改善LC3及LAMP1的mRNA和蛋白水平，提高衰老心肌自噬水平。结论 本研究发现衰老导致的心肌TFEB水平降低严重影响心肌自噬能力，提示TFEB是心肌自噬增龄性减退机制中的关键调节因子。
Abstract:
AIM To explore the role of transcription factor EB (TFEB) in myocardial autophagic decline with aging. METHODS Age-related autophagic and TFEB changes in male C57BL/6 young (4 mo) and aged (22 mo) mice were analyzed. RESULTS Compared with young hearts, the aged heart had a lower level of autophagy (P<0.05). The autophagic markers including Atg5, LC3, Beclin-1 and lysosomal maker LAMP1 decreased in both protein and gene in the aged heart (P<0.05). In addition, cardiomyocyte TFEB, especially in cardiomyocyte nuclei, was significantly reduced in the aged heart (P<0.05), demonstrating that transcriptional activity of cardiomyocyte TFEB declined with aging. Systemic treatment with rapamycin in aged heart partly improved cardiomyocyte nuclear TFEB and autophagy as evidenced by increased autophagosome LC3-II level and increased lysosome LAMP1 level (P<0.05). CONCLUSION We demonstrate that age-related myocardial TFEB decreases significantly affects cardiomyocyte autophagy. TFEB is the key regulatory point of aging-associated myocardial autophagy decline.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2014-11-26.
基金项目：国家自然科学基金项目资助（81170184;81170108;81322004）
通讯作者：李妍，副主任医师，主要从事冠心病基础和临床研究 Email：liyanfmmu@hotmail.com
共同通讯作者：马恒，副教授，主要从事心肌内源性保护机制研究 Email：hengma@fmmu.edu.cn
作者简介：张乐，硕士生 Email：llzhangle@163.com
更新日期/Last Update: 2015-04-28