Decreased intranuclear cardiac troponin I impairs cardiac autophagy through FOS/ATG5 in ageing hearts

作者全名：Liu, Rui Min; Huang, Shan; Hu, Di; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo

作者地址：[Liu, Rui Min; Huang, Shan; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo] Dept Pediat Cardiol, Natl Clin Key Cardiovasc Specialty, Chongqing, Peoples R China; [Liu, Rui Min; Huang, Shan; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Liu, Rui Min; Huang, Shan; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Liu, Rui Min; Huang, Shan; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Liu, Rui Min; Huang, Shan; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo] Chongqing Municipal Hlth Commiss, Key Lab Childrens Important Organ Dev & Dis, Chongqing, Peoples R China; [Liu, Rui Min; Huang, Shan; Liu, Lingjuan; Sun, Hui Chao; Tian, Jie; Pan, Bo] Chongqing Med Univ, Childrens Hosp, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China; [Liu, Rui Min] Capital Med Univ, Beijing Anzhen Hosp, Maternal Fetal Med Ctr Fetal Heart Dis, Beijing, Peoples R China; [Hu, Di] Chongqing Med Univ, Childrens Hosp, Dept Otorhinolaryngol, Chongqing, Peoples R China

通信作者：Pan, B (通讯作者)，Chongqing Med Univ, Childrens Hosp, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China.

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001258431000001

JCR分区：Q2

影响因子：4.3

年份：2024

卷号：28

期号：9

开始页：　

结束页：　

文献类型：Article

关键词：ageing; autophagy; FOS; intranuclear cTnI

摘要：In our previous study, intranuclear cardiac troponin I (cTnI) may function as a co-factor of Yin Yang 1(YY1). Here, we aimed to explore the role of intranuclear cTnI in ageing hearts. Nuclear translocation of cTnI was demonstrated using Western blot and immunofluorescence. The potential nuclear localization sequences (NLSs) of cTnI were predicted by a web server and then verified in 293T cells by putative NLS-eGFP-GST and NLS-mutant transfection. The ratio of Nuclear cTnI/ Total cTnI (Nu/T) decreased significantly in ageing hearts, accompanied with ATG5-decline-related impaired cardiac autophagy. RNA sequencing was performed in cTnI knockout hearts. The differential expressed genes (DEGs) were analysed by overlapping with YY1 ChIP-sequencing data. cTnI gain and loss experiments in vitro determined those filtered DEGs' expression levels. A strong correlation was found between expression patterns cTnI and FOS. Using ChIP-q-PCR, we demonstrated that specific binding DNA sequences of cTnI were enriched in the FOS promoter -299 to -157 region. It was further verified that pcDNA3.1 (-)-cTnI could increase the promoter activity of FOS by using luciferase report assay. At last, we found that FOS can regulate the ATG5 (autophagy-related gene 5) gene by using a luciferase report assay. Taken together, our results indicate that decreased intranuclear cTnI in ageing hearts may cause impaired cardiac autophagy through the FOS/ATG5 pathway.

基金机构：National Natural Science Foundation of China

基金资助正文：The cTnI knockout mice used in the study are gifts from Dr. Huang's laboratory in Florida Atlantic University.