TY - THES AU - László, Eszter TI - A PACAP protektív szerepének vizsgálata a vesében in vitro és in vivo PB - Pécsi Tudományegyetem Általános Orvostudományi Kar PY - 2021 SP - 100 UR - https://m2.mtmt.hu/api/publication/32160444 ID - 32160444 AB - Az ischaemia-reperfusiós vesekárosodás komoly problémát jelent a klinikai gyakorlatban, az acut veseelégtelenség fontos kiváltója lehet, chronicus vesekárosodás kifejlődéséhez vezethet, vagy a már fennálló vesekárosodás végstádiumú veseelégtelenséggé történő progresszióját segítheti elő. Az ischaemiareperfusio kiváltotta vesekárosodás pathofiziológiája rendkívül komplex, melyben egyaránt szerepet kapnak apoptoticus, inflammatoricus folyamatok, valamint az oxidatív stressz. A vese ischaemia-reperfusio egy inflammatoricus kaszkád elindulásához vezet, a gyulladás fő mediátorai chemokinek, melyek a proinflammatoricus citokineket, adhéziós molekulákat, valamint a leukocyták aktivációját szabályozzák. Számos leukocyta-szubtípus aggregatiója kimutatható a peritubularis kapillárisokban, az interstitiumban és a tubulusokban. LA - Hungarian DB - MTMT ER - TY - JOUR AU - László, Eszter AU - Juhász, Tamás AU - Varga, Ádám AU - Czibere, Bernadett AU - Kovács, Krisztina AU - Degrell, Peter AU - Horváth-Opper, Gabriella AU - Jancsó, Gábor AU - Szakály, Péter AU - Tamás, Andrea AU - Reglődi, Dóra TI - Protective Effect of PACAP on Ischemia/Reperfusion-Induced Kidney Injury of Male and Female Rats : Gender Differences JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 68 ET - 0 PY - 2019 IS - 3 SP - 408 EP - 419 PG - 12 SN - 0895-8696 DO - 10.1007/s12031-018-1207-y UR - https://m2.mtmt.hu/api/publication/30321888 ID - 30321888 AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts general cytoprotective effects, including protection in different kidney disorders. The aim of our study was to investigate the ischemia/reperfusion-induced kidney injury of male and female rats to confirm the protective effects of PACAP in the kidney and to reveal possible gender differences.Male and female Wistar rats underwent unilateral renal artery clamping followed by 24-h, 48-h, or 14-day reperfusion. PACAP was administered intravenously before arterial clamping in half of the rats. Tubular damage, cytokine expression pattern, oxidative stress marker, antioxidative status and signaling pathways were evaluated using histology, immunohistology, cytokine array, PCR, and Western blot. Tubular damage was significantly less severe in the PACAP-treated male and female rats compared to controls. Results of female animals were significantly better in both treated and untreated groups. Cytokine expression, oxidative stress marker and antioxidative status confirmed the histological results. We also revealed that PACAP counteracted the decreased PKA phosphorylation, influenced the expression of BMP2 and BMP4, and increased the expression of the protein Smad1.We conclude that PACAP is protective in ischemia/reperfusion-induced kidney injury in both sexes, but females had markedly less pronounced injury after ischemia/reperfusion, possibly also involving further protective factors, the investigation of which could have future therapeutic value in treating ischemic kidney injuries. LA - English DB - MTMT ER - TY - JOUR AU - Horváth-Opper, Gabriella AU - Reglődi, Dóra AU - Czétány, Péter AU - Illés, Anita AU - Rémán, Gyöngyvér Éva AU - Fekete, Andrea AU - Tóth, Gábor AU - László, Eszter AU - Opper, Balázs TI - Effects of Pituitary Adenylate Cyclase Activating Polypeptide in Human Proximal Tubule Cells Against Gentamicin Toxicity JF - INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS J2 - INT J PEPT RES THER VL - 25 PY - 2019 IS - 1 SP - 257 EP - 264 PG - 8 SN - 1573-3149 DO - 10.1007/s10989-017-9666-5 UR - https://m2.mtmt.hu/api/publication/3320609 ID - 3320609 N1 - Funding Agency and Grant Number: Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs/Centre for neuroscience [EFOP-3.6.1.-16-2016-00004]; PTE AOK Research Grant [KA-2016-03, KA-2017-17]; OTKA (NKFIH) [115874, 119759, 2017-1.2.1-NKP-2017-00002]; Bolyai Scholarship [GINOP-2.3.2-15-2016-00050 "PEPSYS", LP2011-08/2011, MTA-TKI 14016]; [EFOP-3.6.2-16-2017-00008] Funding text: EFOP-3.6.1.-16-2016-00004, Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs/Centre for neuroscience, EFOP-3.6.2-16-2017-00008, "The role of neuro-inflammation in neurodegeneration: from molecules to clinics", PTE AOK Research Grant KA-2016-03, KA-2017-17, OTKA (NKFIH) 115874 and 119759, 2017-1.2.1-NKP-2017-00002, Bolyai Scholarship, GINOP-2.3.2-15-2016-00050 "PEPSYS", LP2011-08/2011, MTA-TKI 14016. LA - English DB - MTMT ER - TY - JOUR AU - László, Eszter AU - Varga, Ádám AU - Kovács, Krisztina AU - Jancsó, Gábor AU - Kiss, Péter AU - Tamás, Andrea AU - Szakály, Péter AU - Fülöp, Balázs Dániel AU - Reglődi, Dóra TI - Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice. JF - TRANSPLANTATION PROCEEDINGS J2 - TRANSPLANT PROC VL - 47 PY - 2015 IS - 7 SP - 2210 EP - 2215 PG - 6 SN - 0041-1345 DO - 10.1016/j.transproceed.2015.07.027 UR - https://m2.mtmt.hu/api/publication/2940061 ID - 2940061 AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP-deficient mice to different harmful stimuli. Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney. LA - English DB - MTMT ER - TY - JOUR AU - László, Eszter AU - Kiss, Péter AU - Horváth-Opper, Gabriella AU - Szakály, Péter AU - Tamás, Andrea AU - Reglődi, Dóra TI - The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion. JF - ACTA BIOLOGICA HUNGARICA (1983-2018) J2 - ACTA BIOL HUNG VL - 65 PY - 2014 IS - 4 SP - 369 EP - 378 PG - 10 SN - 0236-5383 DO - 10.1556/ABiol.65.2014.4.1 UR - https://m2.mtmt.hu/api/publication/2788820 ID - 2788820 AB - Pituitary adenylate cyclase activating polypeptide (PACAP ) is a multifunctional neuropeptide occurring in the nervous system as well as in the peripheral organs. Beneficial action of PACAP has been shown in different pathological processes. The strong protective effects of the peptide are probably due to its complex modulatory actions in antiapoptotic, anti-inflammatory and antioxidant pathways. In the kidney, PACAP is protective in models of diabetic nephropathy, myeloma kidney injury, cisplatin-, gentamycin- and cyclosporin-induced damages. Numerous studies have been published describing the protective effect of this peptide in renal ischemia/reperfusion. The present review focuses on the ischemia/reperfusion-induced kidney injury and gives a brief summary about the results published in this area. LA - English DB - MTMT ER - TY - JOUR AU - László, Eszter AU - Kiss, P AU - Szakály, Péter AU - Kovács, K AU - Varga, Ádám AU - Degrell, P AU - Jancsó, Gábor AU - Horváth, G AU - Hashimoto, H AU - Lubics, Andrea AU - Tamás, Andrea AU - Reglődi, Dóra TI - The role of endogenous PACAP in the kidney during ischaemia-reperfusion JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 51 PY - 2013 IS - suppl.1 SP - 215 SN - 0895-8696 UR - https://m2.mtmt.hu/api/publication/2521248 ID - 2521248 N1 - [előadás] LA - English DB - MTMT ER - TY - JOUR AU - Reglődi, Dóra AU - Kiss, Péter AU - Szabadfi, Krisztina AU - Atlasz, Tamás AU - Gábriel, Róbert AU - Horváth-Opper, Gabriella AU - Szakály, Péter AU - Sándor, Balázs Attila AU - Lubics, Andrea AU - László, Eszter AU - Farkas, József AU - Matkovits, Attila AU - Brubel, Réka AU - Hashimoto, H AU - Ferencz, Andrea AU - Vincze, András AU - Helyes, Zsuzsanna AU - Welke, L AU - Lakatos, A AU - Tamás, Andrea TI - PACAP is an endogenous protective factor - insights from PACAP-deficient mice JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 48 PY - 2012 IS - 3 SP - 482 EP - 492 PG - 11 SN - 0895-8696 DO - 10.1007/s12031-012-9762-0 UR - https://m2.mtmt.hu/api/publication/1947674 ID - 1947674 AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin- induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery. LA - English DB - MTMT ER - TY - JOUR AU - Reglődi, Dóra AU - Kiss, Péter AU - Horváth-Opper, Gabriella AU - Lubics, Andrea AU - László, Eszter AU - Tamás, Andrea AU - Rácz, Boglárka AU - Szakály, Péter TI - Effects of pituitary adenylate cyclase activating polypeptide in the urinary system, with special emphasis on its protective effects in the kidney JF - NEUROPEPTIDES J2 - NEUROPEPTIDES VL - 46 PY - 2012 IS - 2 SP - 61 EP - 70 PG - 10 SN - 0143-4179 DO - 10.1016/j.npep.2011.05.001 UR - https://m2.mtmt.hu/api/publication/1708851 ID - 1708851 AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide with diverse effects in the nervous system and peripheral organs. One of the most well-studied effects of PACAP is its cytoprotective action, against different harmful stimuli in a wide variety of cells and tissues. PACAP occurs in the urinary system, from the kidney to the lower urinary tract. The present review focuses on the nephroprotective effects of PACAP and summarizes data obtained regarding the protective effects of PACAP in different models of kidney pathologies. In vitro data show that PACAP protects tubular cells against oxidative stress, myeloma light chain, cisplatin, cyclosporine-A and hypoxia. In vivo data provide evidence for its protective effects in ischemia/reperfusion, cisplatin, cyclosporine-A, myeloma kidney injury, diabetic nephropathy and gentamicin-induced kidney damage. Results accumulated on the renoprotective effects of PACAP suggest that PACAP is an emerging candidate for treatment of human kidney pathologies. LA - English DB - MTMT ER - TY - JOUR AU - László, Eszter AU - Kiss, Péter AU - Reglődi, Dóra AU - Horváth-Opper, Gabriella AU - Lubics, Andrea AU - Tamás, Andrea AU - Brubel, Réka AU - Opper, Balázs AU - Baba, A AU - Hashimoto, H AU - Farkas, József AU - Matkovics, A AU - Magyarlaki, Tamás AU - Helyes, Zsuzsanna AU - Szakály, Péter TI - Effects of in vivo renal ischemia/reperfusion in heterozygous PACAP deficient mice. JF - ACTA PHYSIOLOGICA J2 - ACTA PHYSIOL VL - 202 PY - 2011 IS - S 684 SP - 68 EP - 68 PG - 1 SN - 1748-1708 UR - https://m2.mtmt.hu/api/publication/1740501 ID - 1740501 LA - English DB - MTMT ER - TY - JOUR AU - Horváth-Opper, Gabriella AU - Szakály, Péter AU - László, Eszter AU - Kovács, Krisztina AU - Rácz, Boglárka AU - Ferencz, Andrea AU - Lubics, Andrea AU - Kiss, Péter AU - Tamás, Andrea AU - Brubel, Réka AU - Opper, Balázs AU - Baba, A AU - Hashimoto, H AU - Farkas, József AU - Matkovits, Attila AU - Magyarlaki, Tamás AU - Helyes, Zsuzsanna AU - Reglődi, Dóra TI - Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) show increased susceptibility to in vivo renal ischemia/reperfusion injury. JF - ACTA PHYSIOLOGICA J2 - ACTA PHYSIOL VL - 202 PY - 2011 IS - S684 SP - 44 SN - 1748-1708 UR - https://m2.mtmt.hu/api/publication/1740497 ID - 1740497 LA - English DB - MTMT ER -