PMID- 11433181
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20131121
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 7
IP  - 4
DP  - 2001 Jul-Aug
TI  - Endothelial cell dysfunction in a model of oxidative stress.
PG  - 585-91
AB  - BACKGROUND: We have investigated the role of L-arginine in hyperhomocysteinemia 
      (HHCY). L-arginine is the substrate required for NO production by endothelial NOS 
      (eNOS). When L-arginine is limited, NOS acts principally upon O2 to form 
      superoxide (O2.-). Because HHCY causes formation of reactive oxygen species and 
      reduced endothelial-dependent vasodilation, we hypothesized that HHCY decreases 
      NO formation by limiting the cellular supply of L-arginine. MATERIAL AND METHODS: 
      Studies with cultured bovine aortic endothelial cells (ECs) determined effects of 
      HCY on transport of [3H] L-arginine. Effects on L-arginine transporter protein 
      CAT-1 and eNOS protein were assessed by immunoblotting. Peroxynitrite formation 
      was evaluated by an immunoassay for nitrotyrosine levels. eNOS activity in 
      forming NO was determined by assay for 3H-L-arginine to 3H-citrulline conversion. 
      RESULTS: HCY had a depressive effect on arginine transport in ECs. HCY treatment 
      for a 24 hr period decreased arginine uptake by 27%. HCY treatment for 24 hr 
      significantly reduced cellular levels of the CAT-1 arginine transporter protein ( 
      approximately 30%) and increased nitrotyrosine formation, whereas levels of eNOS 
      protein and basal NOS activity were not altered. Nevertheless, total NO 
      production as indicated by citrulline conversion was significantly decreased. 
      Treatment with the antioxidant N-acetylcysteine reversed the HCY effect on 
      arginine transport, suggesting that transporter oxidation may contribute to the 
      endothelial dysfunction. CONCLUSIONS: The association of HCY-induced decreases in 
      NO formation with decreases in function and expression of the arginine 
      transporter in the absence of alterations in eNOS expression or activity suggests 
      a primary role for arginine transport alterations in HHCY. The action of HCY to 
      reduce arginine uptake may accentuate endothelial dysfunction due to generation 
      of O2.- and peroxynitrite formation, which may cause further oxidative injury.
FAU - Jin, L
AU  - Jin L
AD  - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, 
      Georgia 30912, USA.
FAU - Abou-Mohamed, G
AU  - Abou-Mohamed G
FAU - Caldwell, R B
AU  - Caldwell RB
FAU - Caldwell, R W
AU  - Caldwell RW
LA  - eng
GR  - EY04618/EY/NEI NIH HHS/United States
GR  - EY11766/EY/NEI NIH HHS/United States
GR  - HL52957/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cells, Cultured
MH  - Endothelium, Vascular/cytology/metabolism/*physiopathology
MH  - Homocysteine/*physiology
MH  - *Models, Biological
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type III
MH  - *Oxidative Stress
EDAT- 2001/07/04 10:00
MHDA- 2001/09/21 10:01
CRDT- 2001/07/04 10:00
PHST- 2001/07/04 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/07/04 10:00 [entrez]
AID - 2050 [pii]
PST - ppublish
SO  - Med Sci Monit. 2001 Jul-Aug;7(4):585-91.