title: Effect of PACAP on MAP kinases, Akt and cytokine expressions in rat retinal hypoperfusion.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is known for its potent neuroprotective effects, including the retinoprotective actions in several types of retinal injuries. We have shown earlier that PACAP treatment causes activation of protective pathways and inhibition of pro-apoptotic signaling in excitotoxic retinal lesions. The aim of the present study was to gain insight into the in vivo protective mechanism of PACAP in retinal hypoperfusion injury induced by bilateral common carotid artery occlusion (BCCAO). Rats underwent BCCAO and received intravitreal PACAP (PACAP38) treatment. We investigated the activation level of the protective Akt pathway as well as the different mitogen activated protein kinases (MAPKs) by Western blot analysis and the expression of cytokines using a cytokine array kit. We found that PACAP treatment alone did not influence the phosphorylation of Akt or the MAPKs, but decreased the hypoperfusion-induced activation of both p38MAPK and JNK and increased the activation of the protective Akt and ERK1/2 in hypoperfused retinas. The cytokine profile was dramatically changed after BCCAO, with most cytokines and chemokines showing an increase, which was attenuated by PACAP (such as CINC, CNTF, fractalkine, sICAM, IL-1, LIX, Selectin, MIP-1, RANTES and TIMP-1). In addition, PACAP increased the expression of VEGF and thymus chemokine. The present results provide further insight into the neuroprotective mechanism induced by PACAP in ischemic retinal injuries, showing that PACAP ameliorates hypoperfusion injury involving Akt, MAPK pathways and anti-inflammatory actions.
authors: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors: Aliz
authors: A
authors: Szabo
authors: Bese
authors: B
authors: Danyadi
authors: Eszter
authors: E
authors: Bognar
authors: Krisztina
authors: K
authors: Szabadfi
authors: Eszter
authors: E
authors: Fabian
authors: Peter
authors: P
authors: Kiss
authors: Laszlo
authors: L
authors: Mester
authors: Sridharan
authors: S
authors: Manavalan
authors: Tamas
authors: T
authors: Atlasz
authors: Robert
authors: R
authors: Gabriel
authors: Gabor
authors: G
authors: Toth
authors: Andrea
authors: A
authors: Tamas
authors: Dora
authors: D
authors: Reglodi
authors: Krisztina
authors: K
authors: Kovacs
mesh_terms: D000818:Animals; D017536:Carotid Artery, Common / Q000503:physiopathology; D016893:Carotid Stenosis / Q000150:complications; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D007511:Ischemia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D012171:Retinal Vessels / Q000187:drug effects / Q000503:physiopathology*; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases