C-reactive protein induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of B-cell translocation gene 2 expression.
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.
Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Yuna
Y
Kim
Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jewon
J
Ryu
Department of Biochemistry and Molecular Biology, BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
Min Sook
MS
Ryu
Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sunny
S
Lim
Department of Endocrinology and Metabolism, School of Medicine, Kwandong University, Seoul, Republic of Korea.
Ki Ok
KO
Han
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.
In Kyoung
IK
Lim
Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: steadyhan@amc.seoul.kr.
Ki Hoon
KH
Han
D000818:Animals; D017209:Apoptosis; D002097:C-Reactive Protein / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D059566:M Phase Cell Cycle Checkpoints; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation
D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070114:BTG2 protein, human; D002097:C-Reactive Protein; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases
Apoptosis; Atherogenesis; B-cell translocation gene 2; C-reactive protein; Monocytes; p53