The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involve inhibition of proapoptotic signaling pathways.
Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors are present in the retina and exert several distinct functions. PACAP has well-known neuroprotective effects in neuronal cultures in vitro and against different insults in vivo. Recently we have shown that PACAP is neuroprotective against monosodium glutamate (MSG)-induced retinal degeneration. In the present study we investigated the possible signal transduction pathways involved in the protective effect of intravitreal PACAP administration against apoptotic retinal degeneration induced by neonatal MSG treatment. MSG induced activation of proapoptotic signaling proteins and reduced the levels of antiapoptotic molecules in neonatal retinas. Co-treatment with PACAP attenuated the MSG-induced activation of caspase-3 and JNK, inhibited the MSG-induced cytosolic translocation of apoptosis inducing factor (AIF) and cytochrome c, and increased the level of phospho-Bad. Furthermore, PACAP treatment alone decreased cytosolic AIF and cytochrome c levels, while PACAP6-38 increased cytochrome c release, caspase-3 and JNK activity and decreased phospho-Bad activity. In summary, our results show that PACAP treatment attenuated the MSG-induced changes in apoptotic signaling molecules in vivo and suggest that also endogenously present PACAP has neuroprotective effects. These results may have further clinical implications in reducing glutamate-induced excitotoxicity in several ophthalmic diseases.
Rácz
Boglárka
B
Department of Surgical Research and Techniques, University of Pecs, Hungary.
Gallyas
Ferenc
F
Kiss
Péter
P
Tóth
Gábor
G
Hegyi
Orsolya
O
Gasz
Bálazs
B
Borsiczky
Bálazs
B
Ferencz
Andrea
A
Roth
Erzsebét
E
Tamás
Andrea
A
Lengvári
István
I
Lubics
Andrea
A
Reglodi
Dóra
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012164:Retinal Diseases / Q000139:chemically induced*; D015398:Signal Transduction / Q000187:drug effects*; D012970:Sodium Glutamate / Q000633:toxicity*
D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012970:Sodium Glutamate