Effect of PACAP on MAP kinases, Akt and cytokine expressions in rat retinal hypoperfusion

Szabó, Andrea; Danyadi, B.; Bognar, Eszter; Szabadfi, Krisztina; Fábián, Eszter; Kiss, P.; Mester, L.; Manavalan, Sridharan; Atlasz, Tamás; Gábriel, Róbert; Tóth, Gábor; Tamás, Andrea; Reglődi, Dóra; Kovács, Krisztina

doi:10.1016/j.neulet.2012.06.044

Cited by 41 publications

(44 citation statements)

References 52 publications

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“…In addition, PACAP increased the expression of vascular endothelial growth factor (VEGF) and thymus chemokine. These results provided further insight into the neuroprotective mechanism induced by PACAP in ischemic retinal injuries, showing that PACAP ameliorated hypoperfusion injury involving Akt, MAPK pathways and anti-infl ammatory actions [ 83 ].…”

Section: Ischemic Injury In the Retinamentioning

confidence: 76%

“…In order to elucidate some of the molecular mechanisms, we studied MAP kinases and Akt expression as well as cytokines in BCCAO-induced retinal ischemia in rats [ 83 ]. We revealed that PACAP treatment alone did not infl uence 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.…”

Section: Ischemic Injury In the Retinamentioning

confidence: 97%

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Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide that is well known for its general cytoprotective effects in different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors also occur in the retina. In this review, we summarize the retinoprotective effects of PACAP. In vitro, PACAP is protective against glutamate, thapsigargin, anisomycin, oxidative stress, UV light, high glucose, infl ammation, and anoxia. Both the neural retina and the pigment epithelial cells can be protected by PACAP in various experimental paradigms. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models in rats and mice: excitotoxic injury induced by glutamate, N -methyl-D -aspartate (NMDA) or kainate, ischemic injury induced by carotid artery ligation and high intraocular pressure, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy as well as retinopathy of prematurity. Molecular biological methods have revealed that PACAP activates anti-apoptotic, while inhibits pro-apoptotic signaling pathways, and it also stimulates an anti-infl ammatory environment in the retina. Altogether, PACAP is suggested to be a potential therapeutic retinoprotective agent in various retinal diseases.

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Section: Ischemic Injury In the Retinamentioning

confidence: 76%

Section: Ischemic Injury In the Retinamentioning

confidence: 97%

Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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“…In the retina, PACAP increased anti-infl ammatory cytokine expression [ 53 ]. Furthermore, PACAP led to an anti-infl ammatory cytokine balance in kidney ischemia [ 25 ], in diabetic nephropathy model [ 54 ] and in retinal ischemia [ 55 ].…”

Section: Effects Of Exogenous Pacap In Small Bowel Ischemia-reperfusimentioning

confidence: 99%

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Horváth

Illés

Heimesaat

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia-reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine.

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“…PACAP exerts its protective effects by increasing antiapoptotic factors and decreasing proapoptotic factors in different retinal and other injuries (Martin et al, 2004;Racz et al, 2006;Szabo et al, 2012;Vaudry et al, 2009). PACAP-induced pathways attenuate apoptosis in DR. Four pathways influenced by PACAP (MAPKs, PI3K/Akt, PKC, and inhibiting ER stress) converge to minimize apoptotic damage of retinal neurons in PACAP-treated diabetic retinas.…”

Section: P1025mentioning

confidence: 99%

“…PACAP reduces apoptosis via (iv) elevated level of p-Akt protein and its downstream target GSK3b phosphorylation. Akt signaling seems to play an important role in the neuroprotective effects of PACAP in DR (Szabadfi et al, 2014) and also other different retinal and other injuries (Lazarovici et al, 2012;Li et al, 2005;Racz et al, 2006;Szabo et al, 2012). Most of the cytoprotective effects of PACAP are mediated through activation of PAC1-R, which can induce a signaling cascade to stimulate protective factors and block caspase activation (Seaborn et al, 2011).…”

mentioning

confidence: 99%

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

Szabadfi

Pintér

Reglődi

et al. 2014

International Review of Cell and Molecular Biology

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Any queries or remarks that have arisen during the processing of your manuscript are listed below and are highlighted by flags in the proof. (AU indicates author queries; ED indicates editor queries; and TS/TY indicates typesetter queries.) Please check your proof carefully and answer all AU queries. Mark all corrections and query answers at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file http:// www.elsevier.com/book-authors/science-and-technology-book-publishing/overviewof-the-publishing-process) or compile them in a separate list, and tick off below to indicate that you have answered the query. Please return your input as instructed by the project manager. Location in ChapterQuery / remark AU:1, page 47 Please check the change made in the table title. AU:2, page 57 Citation " Frank et al. (1997)" has not been found in the reference list. Please supply full details for this reference. AU:3, page 58Citation "Wang et al. (2004)" has not been found in the reference list. Please supply full details for this reference. AU:4, page 63The citation "Wang et al. (2010)" has been changed to " Wang et al. (2010)" to match the author name/date in the reference list. Please check here and in subsequent occurrences, and correct if necessary. AU:5, page 3The abbreviations IBA-1 and ZFDM are used only once in the text and they have been deleted in the text. Please consider deleting them from the abbreviation list. B978-0-12-800179-0.00001-5, 00001 IRCMB, 978-0-12-800179-0To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter SPi. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication. AU:6, page 3Please check if all occurrences of "interstitial cell adhesion molecule 1" should be changed to "intercellular adhesion molecule 1." AU:7, page 3Please check the change from "neural" to "neuronal" to match with the text.AU:8, page 3The abbreviation "PKCa" is not used in the text. Please check and delete from the abbreviation list. AU:9, page 9Please check if "retinal ganglion cells (RGCs)" is okay as edited.AU:10, page 13 Please check the change from "retinal circuity" to "retinal circuitry."AU:11, page 17 Please check if "polyamine catabolism" is okay as edited. AU:20, page 46 Please check if edit to sentence starting "The STZ-induced diabetic. . ." is okay. B978-0-12-800179-0.00001-5, 00001 IRCMB, 978-0-12-800179-0To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter SPi. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication. AU:21, page 72Please check if "SST" is okay as edited.AU:2...

show abstract

Effect of PACAP on MAP kinases, Akt and cytokine expressions in rat retinal hypoperfusion

Cited by 41 publications

References 52 publications

Protective Effects of PACAP in the Retina

Protective Effects of PACAP in the Retina

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

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