PMID- 14671039
OWN - NLM
STAT- MEDLINE
DCOM- 20040608
LR  - 20221207
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 19
IP  - 1
DP  - 2004 Jan
TI  - Amadori-configurated albumin induces nitric oxide-dependent apoptosis of 
      endothelial cells: a possible mechanism of diabetic vasculopathy.
PG  - 53-60
AB  - BACKGROUND: We have demonstrated previously that Amadori-configurated glycated 
      albumin (GA) enhances nitric oxide synthase (NOS) activity, and this action may 
      modulate glomerular hyperfiltration in early phases of diabetic nephropathy. 
      Since the late stage of diabetic vasculopathy is characterized by reductions in 
      viable cells within an expanded and disorganized matrix, we tested the hypothesis 
      that GA enhances endothelial cell (EC) apoptosis. METHODS: Murine (t End.1) or 
      human umbilical vein ECs (HUVECs) were incubated with graded GA concentrations 
      (furosine 0.48-96 nmol/ml) at levels that approximated those reported in sera of 
      diabetic patients (76 +/- 0.02 nmol/ml). Apoptosis was evaluated using terminal 
      uridine nick end labelling (TUNEL) to detect DNA fragmentation in gel 
      electrophoresis and p53 expression in immunoperoxidase. Transcription of the 
      inducible (i) and constitutive (c) isoforms of NOS was detected by northern 
      analysis, and total NOS activity was measured as [(3)H]citrulline production from 
      [(3)H]arginine. Cells were also incubated with the NOS inhibitors 
      L-nitromethylarginine (L-NAME) at 0.01 M and aminoguanidine (AMG) at 0.01 M, the 
      protein synthesis inhibitor cycloheximide (CHX) at 1 micro g/ml, and the NO donor 
      sodium nitroprusside (SNP) at 0.01 M. RESULTS: ECs cultured in the presence of GA 
      at furosine concentrations corresponding to levels in diabetic patients showed a 
      significant enhancement of apoptosis. GA also caused parallel dose-dependent 
      increases in iNOS mRNA expression and total NOS activity. The pro-apoptotic 
      effect of GA was inhibited by L-NAME, AMG and CHX, but enhanced by SNP. 
      CONCLUSIONS: We found that Amadori-configurated GA at furosine concentrations 
      similar to those in diabetic patients favoured EC apoptosis through enhancement 
      of iNOS activity. We propose that this process may be involved in the progressive 
      cellular loss occurring in vascular and glomerular diabetic sclerosis.
FAU - Amore, Alessandro
AU  - Amore A
AD  - Nephrology, Dialysis and Transplantation Department, Regina Margherita Children's 
      Hospital, Piazza Polinia 94, 10126 Turin, Italy. 
      amorenefro@oirmsantanna.piemonte.it
FAU - Cirina, Paola
AU  - Cirina P
FAU - Conti, Giovanni
AU  - Conti G
FAU - Cerutti, Franco
AU  - Cerutti F
FAU - Bagheri, Nayer
AU  - Bagheri N
FAU - Emancipator, Steven Noel
AU  - Emancipator SN
FAU - Coppo, Rosanna
AU  - Coppo R
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Serum Albumin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - 0 (Glycated Serum Albumin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Diabetic Angiopathies/*physiopathology
MH  - Diabetic Nephropathies/*physiopathology
MH  - Endothelial Cells/*physiology
MH  - Glycation End Products, Advanced/biosynthesis
MH  - Humans
MH  - Mice
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Serum Albumin/*metabolism
MH  - Glycated Serum Albumin
EDAT- 2003/12/13 05:00
MHDA- 2004/06/21 10:00
CRDT- 2003/12/13 05:00
PHST- 2003/12/13 05:00 [pubmed]
PHST- 2004/06/21 10:00 [medline]
PHST- 2003/12/13 05:00 [entrez]
AID - 10.1093/ndt/gfg428 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2004 Jan;19(1):53-60. doi: 10.1093/ndt/gfg428.