Early changes in pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and related receptors expression in retina of streptozotocin-induced diabetic rats.
The retinal expression and distribution of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) and their receptors was investigated in early streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in rats by STZ injection (60 mg/kg i.p.). PACAP, VIP and their receptors in nondiabetic control and diabetic retinas were assayed by quantitative real-time PCR and Western blot 1 and 3 weeks after STZ injection. Effects of intravitreal treatment with PACAP38 on the expression of the two apoptotic-related genes Bcl-2 and p53 were also evaluated. PACAP and VIP, as well as VPAC1 and VPAC2 receptors, but not PAC1 mRNA levels, were transiently induced in retinas 1 week following STZ. These findings were confirmed by immunoblot analyses. Three weeks after the induction of diabetes, significant decreases in the expression of peptides and their receptors were observed, Bcl-2 expression decreased and p53 expression increased. Intravitreal injection of PACAP38 restored STZ-induced changes in retinal Bcl-2 and p53 expression to nondiabetic levels. The initial upregulation of PACAP, VIP and related receptors and the subsequent downregulation in retina of diabetic rats along with the protective effects of PACAP38 treatment, suggest a role for both peptides in the pathogenesis of diabetic retinopathy.
Department of Bio-Medical Sciences Catania, Italy.
Salvatore
S
Giunta
Alessandro
A
Castorina
Claudio
C
Bucolo
Gaetano
G
Magro
Filippo
F
Drago
Velia
V
D'Agata
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose; D017931:DNA Primers / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D058449:Intravitreal Injections; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D013311:Streptozocin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D001786:Blood Glucose; D017931:DNA Primers; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D019253:Proto-Oncogene Proteins c-bcl-2; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D016159:Tumor Suppressor Protein p53; D014660:Vasoactive Intestinal Peptide; D013311:Streptozocin