title: Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Oxidative Stress in Zebrafish Hair Cells.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide, with known antiapoptotic functions. Our previous in vitro study has demonstrated the ameliorative role of PACAP-38 in chicken hair cells under oxidative stress conditions, but its effects on living hair cells is now yet known. Therefore, the aim of the present study was to investigate in vivo the protective role of PACAP-38 in hair cells found in zebrafish (Danio rerio) sense organs-neuromasts. To induce oxidative stress the 5-day postfertilization (dpf) zebrafish larvae were exposed to 1.5 mM H2O2for 15 min or 1 h. This resulted in an increase in caspase-3 and p-38 MAPK level in the hair cells as well as in an impairment of the larvae basic behavior. To investigate the ameliorative role of PACAP-38, the larvae were incubated with a mixture of 1.5 mM H2O2and 100 nM PACAP-38 following 1 h preincubation with 100 nM PACAP-38 only. PACAP-38 abilities to prevent hair cells from apoptosis were investigated. Whole-mount immunohistochemistry and confocal microscopy analyses revealed that PACAP-38 treatment decreased the cleaved caspase-3 level in the hair cells, but had no influence on p-38 MAPK. The analyses of basic locomotor activity supported the protective role of PACAP-38 by demonstrating the improvement of the fish behavior after PACAP-38 treatment. In summary, our in vivo findings demonstrate that PACAP-38 protects zebrafish hair cells from oxidative stress by attenuating oxidative stress-induced apoptosis.
authors: Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, box 105J, 10-719, Olsztyn, Poland. natalia_kasica@wp.pl.
authors: Natalia
authors: 0000-0002-0242-2587
authors: N
authors: Kasica
authors: Department of Pathophysiology, Forensic Veterinary and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-719, Olsztyn, Poland.
authors: Piotr
authors: P
authors: Podlasz
authors: Department of Anatomy, Neuroscience Center, University of Helsinki, Haartmaninkatu 8 (Biomedicum Helsinki), 00290, Helsinki, Finland.
authors: Maria
authors: M
authors: Sundvik
authors: Department of Anatomy, University of Pecs, Szigeti 12, 7624, Pecs, Hungary.
authors: Andrea
authors: A
authors: Tamas
authors: Department of Anatomy, University of Pecs, Szigeti 12, 7624, Pecs, Hungary.
authors: Dora
authors: D
authors: Reglodi
authors: Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, box 105J, 10-719, Olsztyn, Poland.
authors: Jerzy
authors: J
authors: Kaleczyc
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D000066829:Neuroprotection / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Antioxidant; Apoptosis; Behavior; Hydrogen peroxide; Neuromast; PACAP