The p65 subunit of NF-κB involves in RIP140-mediated inflammatory and metabolic dysregulation in cardiomyocytes.
The transcription factor NF-κB regulates expression of many genes that are involved in inflammation, fatty acid and glucose metabolism, and plays a crucial role in cardiac pathological processes. RIP140 is a corepressor that down-regulates expression of genes involved in the cellular substrate uptake and mitochondrial β-oxidation. In addition to this, RIP140 also acts as a coactivator for p65-NF-κB, potentiating the secretion of proinflammatory cytokines in macrophages, but the effects in cardiomyocytes are still unknown. In this study, overexpression of RIP140 induced proinflammatory gene expression and cytokine release in neonatal rat cardiomyocytes, which could be reversed by p65-NF-κB inhibition. Furthermore, RIP140-mediated repression of metabolic-related genes, mitochondrial biogenesis and metabolic function were weakened after knocking down of p65-NF-κB. These findings suggest that p65-NF-κB plays an important role in RIP140-mediated proinflammatory response and energy metabolism in cardiomyocytes, and provide evidence for the crosstalk between proinflammatory processes and metabolic dysregulation in the heart.
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Luankun
L
Zhang
Department of Pharmacy, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, PR China.
Yanfang
Y
Chen
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Zhongbao
Z
Yue
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Yanhong
Y
He
Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu 611130, PR China.
Jian
J
Zou
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Shaorui
S
Chen
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Min
M
Liu
Department of Pharmacy, Changsha Central Hospital, Changsha 410004, PR China.
Xi
X
Chen
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Zhiping
Z
Liu
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Xueping
X
Liu
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Xiaojun
X
Feng
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Min
M
Li
Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China. Electronic address: liupq@mail.sysu.edu.cn.
Peiqing
P
Liu
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004734:Energy Metabolism / Q000235:genetics; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000078723:Nuclear Receptor Interacting Protein 1; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D018836:Inflammation Mediators; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D011994:Recombinant Proteins; C498145:Rela protein, rat; D051996:Transcription Factor RelA
Cardiac energy metabolism; Inflammation; Mitochondria; NF-κB; RIP140