PMID- 12627328
OWN - NLM
STAT- MEDLINE
DCOM- 20031205
LR  - 20181113
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 46
IP  - 2
DP  - 2003 Feb
TI  - Pigment epithelium-derived factor prevents advanced glycation end 
      products-induced monocyte chemoattractant protein-1 production in microvascular 
      endothelial cells by suppressing intracellular reactive oxygen species 
      generation.
PG  - 284-7
AB  - AIMS/HYPOTHESIS: Monocytes and macrophages accumulate in the lesion of the 
      diabetic retina, which are most likely involved in the progression of diabetic 
      retinopathy. The levels of monocyte chemoattractant protein-1 (MCP-1) in vitreous 
      fluids were associated with the severity of proliferative diabetic retinopathy. 
      Recently, pigment epithelium-derived factor has been shown to be involved in the 
      pathogenesis of proliferative diabetic retinopathy. However, a role of pigment 
      epithelium-derived factor in monocyte recruitments in diabetic retinopathy 
      remains to be elucidated. In this study, we investigated effects of purified 
      pigment epithelium-derived factor on AGE-induced reactive oxygen species 
      generation, MCP-1 mRNA up-regulation and protein production in human cultured 
      microvascular endothelial cells. METHODS: The intracellular formation of reactive 
      oxygen species was measured using the fluorescent probe CM-H(2)DCFDA. MCP-1 gene 
      expression was analysed in quantitative reverse transcription-polymerase chain 
      reaction. Monocyte chemoattractant protein-1 production by microvascular 
      endothelial cells was measured with an ELISA system. RESULTS: AGE increased 
      intracellular reactive oxygen species generation in microvascular endothelial 
      cells. Pigment epithelium-derived factor inhibited the AGE-induced reactive 
      oxygen species generation in a dose-dependent manner. An anti-oxidant, 
      N-acetylcysteine, or pigment epithelium-derived factor completely prevented the 
      AGE-induced up-regulation of MCP-1 mRNA contents as well as protein production in 
      microvascular endothelial cells. CONCLUSIONS/INTERPRETATIONS: Pigment 
      epithelium-derived factor inhibits the AGE-induced reactive oxygen species 
      generation and the subsequent increase in MCP-1 production in microvascular 
      endothelial cells. Our study suggests that substitution of pigment 
      epithelium-derived factor could prevent the progression of diabetic retinopathy 
      by attenuating the deleterious effects of AGE.
FAU - Inagaki, Y
AU  - Inagaki Y
AD  - Division of Endocrinology and Metabolism, Kurume University School of Medicine, 
      Kurume 830-0011, Japan.
FAU - Yamagishi, S
AU  - Yamagishi S
FAU - Okamoto, T
AU  - Okamoto T
FAU - Takeuchi, M
AU  - Takeuchi M
FAU - Amano, S
AU  - Amano S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030111
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Chemokine CCL2)
RN  - 0 (Eye Proteins)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Serpins)
RN  - 0 (pigment epithelium-derived factor)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/*antagonists & inhibitors/biosynthesis/genetics
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism
MH  - *Eye Proteins
MH  - Gene Expression/drug effects
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Humans
MH  - Intracellular Membranes/*metabolism
MH  - *Nerve Growth Factors
MH  - Proteins/*pharmacology
MH  - Reactive Oxygen Species/*antagonists & inhibitors
MH  - Serpins/*pharmacology
EDAT- 2003/03/11 04:00
MHDA- 2003/12/06 05:00
CRDT- 2003/03/11 04:00
PHST- 2002/06/10 00:00 [received]
PHST- 2002/09/10 00:00 [revised]
PHST- 2003/03/11 04:00 [pubmed]
PHST- 2003/12/06 05:00 [medline]
PHST- 2003/03/11 04:00 [entrez]
AID - 10.1007/s00125-002-1013-4 [doi]
PST - ppublish
SO  - Diabetologia. 2003 Feb;46(2):284-7. doi: 10.1007/s00125-002-1013-4. Epub 2003 Jan 
      11.