PMID- 24238298
OWN - NLM
STAT- MEDLINE
DCOM- 20140708
LR  - 20211021
IS  - 1476-511X (Electronic)
IS  - 1476-511X (Linking)
VI  - 12
DP  - 2013 Nov 16
TI  - Reduced beta2-glycoprotein I protects macrophages from ox-LDL-induced foam cell 
      formation and cell apoptosis.
PG  - 174
LID - 10.1186/1476-511X-12-174 [doi]
AB  - BACKGROUND: Reduced beta2-glycoprotein I (beta2-GPI) is a free thiol-containing 
      form of beta2-GPI that displays a powerful effect in protecting endothelial cells 
      from oxidative stress-induced cell death. The present study aims to investigate 
      the effect of beta2-GPI or reduced beta2-GPI on ox-LDL-induced foam cell 
      formation and on cell apoptosis and to determine the possible mechanisms. 
      METHODS: The RAW264.7 macrophage cell line was selected as the experimental 
      material. Oil red O staining and cholesterol measurement were used to detect 
      cholesterol accumulation qualitatively and quantitatively, respectively. Flow 
      cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used 
      to detect the mRNA expression of the main proteins that are associated with the 
      transport of cholesterol, such as CD36, SRB1, ABCA1 and ABCG1. Western blot 
      analysis was used to detect the protein expression of certain apoptosis-related 
      proteins, such as caspase-9, caspase-3, p38 MAPK/p-p38 MAPK and JNK/p-JNK. 
      RESULTS: Beta2-GPI or reduced beta2-GPI decreased ox-LDL-induced cholesterol 
      accumulation (96.45 +/- 8.51 mug/mg protein vs. 114.35 +/- 10.38 mug/mg protein, 
      p < 0.05;74.44 +/- 5.27 mug/mg protein vs. 114.35 +/- 10.38 mug/mg protein, p < 0.01) 
      and cell apoptosis (30.00 +/- 5.10% vs. 38.70 +/- 7.76%, p < 0.05; 20.66 +/- 2.50% vs. 
      38.70 +/- 7.76%, p < 0.01), and there are significant differences between beta2-GPI 
      and reduced beta2-GPI (p < 0.05). Reduced beta2-GPI decreased the ox-LDL-induced 
      expression of CD36 mRNA and ABCA1 mRNA (p < 0.05), as well as CD36, cleaved 
      caspase-9, cleaved caspase-3, p-p38 MAPK and p-JNK proteins (p < 0.05 or 
      p < 0.01). Beta2-GPI did not significantly decrease the expression of ABCA1 mRNA 
      and the p-p38 MAPK protein. CONCLUSIONS: Both beta2-GPI and reduced beta2-GPI 
      inhibit ox-LDL-induced foam cell formation and cell apoptosis, and the latter 
      exhibits a stronger inhibition effect. Both of these glycoproteins reduce the 
      lipid intake of macrophages by downregulating CD36 as well as protein expression. 
      Reduced beta2-GPI inhibits cell apoptosis by reducing the ox-LDL-induced 
      phosphorylation of p38 MAPK and JNK, and the amount of cleaved caspase-3 and 
      caspase-9. Beta2-GPI does not inhibit the ox-LDL-induced phosphorylation of p38 
      MAPK.
FAU - Wang, Wei-Lin
AU  - Wang WL
FAU - Meng, Zhen-Xing
AU  - Meng ZX
FAU - Zhou, Sai-Jun
AU  - Zhou SJ
FAU - Li, Chun-Jun
AU  - Li CJ
FAU - Chen, Rui
AU  - Chen R
FAU - Lv, Lin
AU  - Lv L
FAU - Ma, Ze-Jun
AU  - Ma ZJ
FAU - Yu, De-Min
AU  - Yu DM
AD  - 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, the Key 
      Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases 
      Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, 
      300070, Tianjin, China. yudemintij@126.com.
FAU - Yu, Pei
AU  - Yu P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131116
PL  - England
TA  - Lipids Health Dis
JT  - Lipids in health and disease
JID - 101147696
RN  - 0 (ABCA1 protein, mouse)
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CD36 Antigens)
RN  - 0 (Lipoproteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Scarb1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 0 (oxidized low density lipoprotein)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/genetics/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/genetics/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Biological Transport/drug effects
MH  - CD36 Antigens/antagonists & inhibitors/genetics/metabolism
MH  - Caspases/genetics/metabolism
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cholesterol/*metabolism
MH  - Foam Cells/*drug effects/metabolism/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Lipoproteins/genetics/metabolism
MH  - Lipoproteins, LDL/antagonists & inhibitors/*pharmacology
MH  - MAP Kinase Kinase 4/genetics/metabolism
MH  - Mice
MH  - Oxidation-Reduction
MH  - Phosphorylation/drug effects
MH  - Scavenger Receptors, Class B/genetics/metabolism
MH  - Signal Transduction
MH  - beta 2-Glycoprotein I/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
PMC - PMC3842777
EDAT- 2013/11/19 06:00
MHDA- 2014/07/09 06:00
PMCR- 2013/11/16
CRDT- 2013/11/19 06:00
PHST- 2013/08/10 00:00 [received]
PHST- 2013/11/11 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/07/09 06:00 [medline]
PHST- 2013/11/16 00:00 [pmc-release]
AID - 1476-511X-12-174 [pii]
AID - 10.1186/1476-511X-12-174 [doi]
PST - epublish
SO  - Lipids Health Dis. 2013 Nov 16;12:174. doi: 10.1186/1476-511X-12-174.