01 January 2001
Endothelial cell dysfunction in a model of oxidative stress.
Liming Jin, Gamal Abou-Mohamed, Ruth B Caldwell, William R CaldwellMed Sci Monit 2001; 7(4): BR585-591 :: ID: 421099
Abstract
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-arginineis limited, NOS acts principally upon O2 to form superoxide (O2.-). Because HHCY causes formation ofreactive oxygen species and reduced endothelial-dependent vasodilation, we hypothesized that HHCY decreasesNO formation by limiting the cellular supply of L-arginine.MATERIAL AND METHODS: Studies with culturedbovine aortic endothelial cells (ECs) determined effects of HCY on transport of [3H] L-arginine. Effectson L-arginine transporter protein CAT-1 and eNOS protein were assessed by immunoblotting. Peroxynitriteformation was evaluated by an immunoassay for nitrotyrosine levels. eNOS activity in forming NO was determinedby assay for 3H-L-arginine to 3H-citrulline conversion.RESULTS: HCY had a depressive effect on argininetransport in ECs. HCY treatment for a 24 hr period decreased arginine uptake by 27%. HCY treatment for24 hr significantly reduced cellular levels of the CAT-1 arginine transporter protein ( approximately30%) and increased nitrotyrosine formation, whereas levels of eNOS protein and basal NOS activity werenot altered. Nevertheless, total NO production as indicated by citrulline conversion was significantlydecreased. Treatment with the antioxidant N-acetylcysteine reversed the HCY effect on arginine transport,suggesting that transporter oxidation may contribute to the endothelial dysfunction.CONCLUSIONS: Theassociation of HCY-induced decreases in NO formation with decreases in function and expression of thearginine transporter in the absence of alterations in eNOS expression or activity suggests a primaryrole for arginine transport alterations in HHCY. The action of HCY to reduce arginine uptake may accentuateendothelial dysfunction due to generation of O2.- and peroxynitrite formation, which may cause furtheroxidative injury.
Keywords: Hyperhomocysteinemia, L-arginine uptake, endothelial cell dysfunction,
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
26 Feb 2024 : Clinical Research
Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in...Med Sci Monit In Press; DOI: 10.12659/MSM.942509
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952