PMID- 11912219
OWN - NLM
STAT- MEDLINE
DCOM- 20020712
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 23
DP  - 2002 Jun 7
TI  - Advanced glycation end product-induced apoptosis and overexpression of vascular 
      endothelial growth factor and monocyte chemoattractant protein-1 in 
      human-cultured mesangial cells.
PG  - 20309-15
AB  - Advanced glycation end products (AGE) have been implicated in the pathogenesis of 
      glomerulosclerosis in diabetes. However, their involvement in the development of 
      the early phase of diabetic nephropathy has not been fully elucidated. We 
      investigated the effects of AGE on growth and on vascular endothelial growth 
      factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) expression in human 
      cultured mesangial cells. We prepared three immunochemically distinct AGE by 
      incubating bovine serum albumin (BSA) with glucose, glyceraldehyde, or 
      glycolaldehyde. When human mesangial cells were cultured with various types of 
      AGE-BSA, viable cell numbers as well as DNA syntheses were significantly 
      decreased. All of the AGE-BSA were found to significantly increase p53 and Bax 
      protein accumulations and subsequently induce apoptotic cell death in mesangial 
      cells. An antioxidant, N-acetylcysteine, significantly prevented the AGE-induced 
      apoptotic cell death in mesangial cells. Human mesangial cells stimulated 
      prostacyclin production by co-cultured glomerular endothelial cells. Furthermore, 
      various types of AGE-BSA were found to up-regulate the levels of mRNAs for VEGF 
      and stimulate the secretion of VEGF and MCP-1 proteins in mesangial cells. The 
      results suggest that AGE disturbed glomerular homeostasis by inducing apoptotic 
      cell death in mesangial cells and elicited hyperfiltration and microalbuminuria 
      by stimulating the secretion of VEGF and MCP-1 proteins, thereby being involved 
      in the pathogenesis of the early phase of diabetic nephropathy.
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Kurume 
      University School of Medicine, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
FAU - Inagaki, Yosuke
AU  - Inagaki Y
FAU - Okamoto, Tamami
AU  - Okamoto T
FAU - Amano, Shinjiro
AU  - Amano S
FAU - Koga, Kohachiro
AU  - Koga K
FAU - Takeuchi, Masayoshi
AU  - Takeuchi M
FAU - Makita, Zenji
AU  - Makita Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020323
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Lymphokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Apoptosis/*physiology
MH  - Cell Division
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Coculture Techniques
MH  - Diabetic Nephropathies/metabolism
MH  - Endothelial Growth Factors/*genetics
MH  - Glomerular Mesangium/cytology/*metabolism
MH  - Glycation End Products, Advanced/*physiology
MH  - Humans
MH  - Lymphokines/*genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2002/03/26 10:00
MHDA- 2002/07/13 10:01
CRDT- 2002/03/26 10:00
PHST- 2002/03/26 10:00 [pubmed]
PHST- 2002/07/13 10:01 [medline]
PHST- 2002/03/26 10:00 [entrez]
AID - S0021-9258(20)84871-6 [pii]
AID - 10.1074/jbc.M202634200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Jun 7;277(23):20309-15. doi: 10.1074/jbc.M202634200. Epub 2002 
      Mar 23.