title: Control of peroxyntrite-induced production of inducible nitric oxide synthase isoforms and antagonism of cholecystokinin octapeptide -8 in retinal pigment epithelial cells in vivo.
abstract: OBJECTIVE
  To explore if peroxyntrite (ONOO(-)) induced iNOS via Fas/Fas/L pathway in diabetic rats and the effection of cholecystokinin octapeptide-8 (CCK-8) as therapeutic agent for decrease diabetic retinopathy.
  
  
  METHODS
  Thirty-six rats were taken as control group, seventy two were given (streptozotocin) STZ (45mg/kg) and then divided into ONOO(-) group and CCK-8 group (peritoneal injection CCK-8). STZ-induced diabetic rats were treated with CCK-8 for 60 days. Western blotting analysis, DNA ladder, RT-PCR, immunohistochemistry and flow cytometry were used for determining the expression of nitrotyrosine (NT, the foot print of ONOO(-)); apoptosis and inducible nitric oxide synthase (iNOS) mRNA as well as Fas/Fasl signal transduction in RPE cells.
  
  
  RESULTS
  Both RPE cells in ONOO(-) and CCK-8 group developed apoptosis and expressed NT, iNOS mRNA and Fas/Fasl. But latter delayed the all changes in a time-dependent manner compared with control and ONOO(-) group (P<0.001). iNOS and Fas/Fasl were up-regulated and associated with an increase of expression of ONOO(-)in vivo.
  
  
  CONCLUSIONS
  The study suggested that apoptosis of RPE was partly induced by ONOO(-) may be the new way of oxidative damage to the RPE cells. CCK-8 decreased RPE cells apoptosis partly induced by ONOO(-) and is a potential drug for therapy of diabetic retinopathy. The mechanism of CCK-8 dealing with RPE cells may be related to its direct inhibition of the formation of iNOS to produce ONOO(-) and antagnism of damage of ONOO(-) to RPE cells.
authors.affiliation: Ophthalmology Department of Hebei Province People's Hospital, Shijiazhuang 050051, Hebei Province, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Hao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang