Aberrant utilization of nitric oxide and regulation of soluble guanylate cyclase in rat diabetic retinopathy.
Antioxid Redox Signal
; 5(4): 457-65, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-13678534
ABSTRACT
Although nitric oxide (NO) was shown not only to exert biological activities through activation of soluble guanylate cyclase (sGC), but also to cause oxidative stress, mechanisms for switching these pathways are unknown. This study aimed to examine aberrant utilization of NO under disease conditions such as diabetes mellitus. Diabetes was induced in male Wistar rats by injecting streptozotocin (STZ; 50 mg/kg body weight, i.p.). Retina was perfusion-fixed for immunohistochemistry to detect the gas-mediated activation of sGC by anti-sGC antibodies that are function-sensitive [monoclonal antibody (MoAb) 3221] and -insensitive (MoAb28131). Regional lipid peroxidation was also examined by an anti-acrolein MoAb. At 6 weeks after STZ injection, inducible NO synthase induction became evident, coinciding with the overproduction of nitrotyrosine, followed by that of acrolein. Despite such NO overproduction, sGC did not exhibit any notable activation. When STZ-treated animals were posttreated with a derivative of superoxide dismutase that stays in circulation without undergoing renal ultrafiltration, immunoreactivities to MoAb3221 but not to MoAb28131 increased markedly in diabetic retina, suggesting that superoxide cancels free NO for local sGC activation. These results provide evidence of aberrant utilization of NO and suggest that superoxide plays a role in interfering with NO-mediated sGC activation for phototransducing events in this neural tissue.
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Base de dados:
MEDLINE
Assunto principal:
Retinopatia Diabética
/
Guanilato Ciclase
/
Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Antioxid Redox Signal
Assunto da revista:
METABOLISMO
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Japão