PMID- 12899782
OWN - NLM
STAT- MEDLINE
DCOM- 20040105
LR  - 20171116
IS  - 0376-2491 (Print)
IS  - 0376-2491 (Linking)
VI  - 83
IP  - 12
DP  - 2003 Jun 25
TI  - [Advanced glycation end products stimulate human endothelial cells to produce 
      monocyte chemoattractant protein-1].
PG  - 1075-9
AB  - OBJECTIVE: To investigate the effects of advanced glycation end products (AGE) on 
      secretion of monocyte chemoattractant protein-1 (MCP-1) by human endothelial 
      cells and its signal transduction pathway. METHODS: Human umbilical vein 
      endothelial cells (HUVECs) and HUVEC-derived cell line (ECV304) were cultured in 
      vitro with indicated concentration of AGE modified human serum albumin (AGE-HSA) 
      or AGE modified bovine serum albumin (AGE-BSA). The production of MCP-1 was 
      evaluated by Western blotting and enzyme-linked immunoadsorbent assay (ELISA). 
      The MCP-1 mRNA expression was assayed by reverse-transcription polymerase chain 
      reaction (RT-PCR). Intracellular oxidative stress was detected by flow cytometry. 
      The phosphorylation activity of cellular p38 mitogen-activated protein kinase 
      (p38-MAPK) was analyzed by Western blotting using a phospho-specific antibody. 
      RESULTS: AGE-HSA and AGE-BSA, but not their unmodified form, upregulated the 
      expression of MCP-1 mRNA and protein dose- and time-dependently. The MCP-1 
      concentration in the supernatant of HUVECs incubated with 50 micro g/ml AGE-HSA 
      for 12 hours increased from 48.3 pg/ micro g +/- 0.6 pg/ micro g protein to 148.1 
      pg/ micro g +/- 12.6 pg/ micro g protein (P < 0.01). AGE modified proteins were 
      associated with enhanced oxidative stress and p38-MAPK phosphorylation activity. 
      Incubation of HUVECs with 50 micro g/ml AGE-HSA for 30 minutes resulted in 
      increase of p38-MAPK phosphorylation activity by 91% +/- 14% (P < 0.01). 
      Antioxidant or SB 203580, a specific inhibitor of p38, could block the 
      over-expression of MCP-1. CONCLUSION: AGE modified proteins stimulate endothelial 
      cells to produce MCP-1 through activation of the p38 signal pathway. This effect 
      may contribute to the pathogenesis of atherosclerosis seen in AGE-associated 
      diseases.
FAU - Guo, Zhi-jian
AU  - Guo ZJ
AD  - Department of Nephrology, Nanfang Hospital, First Military Medical University, 
      Guangzhou 510515, China.
FAU - Hou, Fan-fan
AU  - Hou FF
FAU - Liang, Min
AU  - Liang M
FAU - Wang, Li
AU  - Wang L
FAU - Zhang, Xun
AU  - Zhang X
FAU - Liu, Zhi-qiang
AU  - Liu ZQ
LA  - chi
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Yi Xue Za Zhi
JT  - Zhonghua yi xue za zhi
JID - 7511141
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serum Albumin)
RN  - 0 (advanced glycation end products-bovine serum albumin)
RN  - 0 (advanced glycation end products-human serum albumin)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/analysis
MH  - Serum Albumin/*pharmacology
MH  - Serum Albumin, Bovine/*pharmacology
MH  - Serum Albumin, Human
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2003/08/06 05:00
MHDA- 2004/01/06 05:00
CRDT- 2003/08/06 05:00
PHST- 2003/08/06 05:00 [pubmed]
PHST- 2004/01/06 05:00 [medline]
PHST- 2003/08/06 05:00 [entrez]
PST - ppublish
SO  - Zhonghua Yi Xue Za Zhi. 2003 Jun 25;83(12):1075-9.