C-reactive protein induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of B-cell translocation gene 2 expression

Yuna Kim; Jewon Ryu; Min Sook Ryu; Sunny Lim; Ki Ok Han; In Kyoung Lim; Ki Hoon Han

doi:10.1016/j.febslet.2014.01.008

C-reactive protein induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of B-cell translocation gene 2 expression

FEBS Lett. 2014 Feb 14;588(4):625-31. doi: 10.1016/j.febslet.2014.01.008. Epub 2014 Jan 17.

Authors

Yuna Kim¹, Jewon Ryu¹, Min Sook Ryu², Sunny Lim¹, Ki Ok Han³, In Kyoung Lim⁴, Ki Hoon Han⁵

Affiliations

¹ Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² Department of Biochemistry and Molecular Biology, BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
³ Department of Endocrinology and Metabolism, School of Medicine, Kwandong University, Seoul, Republic of Korea.
⁴ Department of Biochemistry and Molecular Biology, BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon 443-721, Republic of Korea. Electronic address: iklim@ajou.ac.kr.
⁵ Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: steadyhan@amc.seoul.kr.

PMID: 24440351
DOI: 10.1016/j.febslet.2014.01.008

Abstract

We hypothesized that C-reactive protein (CRP) may affect the cell cycle and induce apoptotic changes of monocytes. CRP (∼25 μg/ml) significantly increased expressions of B-cell translocation gene 2 (BTG2) mRNA and protein in human monocytes through pathways involving CD32/NADPH oxidase 2/p53, which eventually induced G2/M phase arrest and apoptotic cell death. Such pro-apoptotic effect of CRP was not found in thioglycollate-elicited intraperitoneal monocytes/macrophages harvested from BTG2-knockout male C57BL/6 mice (n=5). Within atheromatous plaques obtained from CRP-transgenic male LDLR(-/-) C57BL/6 mice (n=5) and human coronary arteries, BTG2 co-localized with CRP, p53 and monocytes/macrophages. Therefore the pro-apoptotic pathway of CRP-CD32-Nox2-p53-BTG2 may contribute to the retardation of the atherogenic process.

Keywords: Apoptosis; Atherogenesis; B-cell translocation gene 2; C-reactive protein; Monocytes; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis*
C-Reactive Protein / metabolism*
G2 Phase Cell Cycle Checkpoints*
Humans
Immediate-Early Proteins / genetics*
M Phase Cell Cycle Checkpoints*
Male
Membrane Glycoproteins / metabolism
Mice
Monocytes / cytology*
NADPH Oxidase 2
NADPH Oxidases / metabolism
Reactive Oxygen Species / metabolism
Receptors, IgG / metabolism
Tumor Suppressor Protein p53 / metabolism
Tumor Suppressor Proteins / genetics*
Up-Regulation*

Substances

Immediate-Early Proteins
Membrane Glycoproteins
Reactive Oxygen Species
Receptors, IgG
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
BTG2 protein, human
C-Reactive Protein
CYBB protein, human
NADPH Oxidase 2
NADPH Oxidases