Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Oxidative Stress in Zebrafish Hair Cells

Kasica, Natalia; Podlasz, Piotr; Sundvik, Maria; Tamás, Andrea; Reglődi, Dóra; Kaleczyc, Jerzy

doi:10.1007/s12640-016-9659-8

Cited by 14 publications

(15 citation statements)

References 96 publications

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“…PACAP-38 was synthesized by the solid-phase technique utilizing t Boc chemistry [ 25 ] as described previously [ 26 ]. The sequence of PACAP-38 used in the current study referred to mammalian PACAP-38 demonstrating 80% homology between the zebrafish and human peptide sequence and the zebrafish receptor binding site sequence corresponded to that of humans in almost 100% [ 6 ].…”

Section: Methodsmentioning

confidence: 99%

“…Pituitary adenylate cyclase–activating polypeptide (PACAP-38) is a pleiotropic neuropeptide, with known protective and anti-apoptotic functions [ 1 – 6 ]. In recent decades, PACAP-38 has been also classified as an anti-inflammatory factor which regulates inflammatory responses via influencing both anti- and pro-inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

“…Our previous contributions have demonstrated that PACAP-38 plays an anti-apoptotic role in oxidative stress-damaged zebrafish hair cells, which is very promising information in the context of (as far as) working out suitable models for studying PACAP-38 properties in ototoxicity screening assays [ 6 ]. The zebrafish lateral line (posterior and anterior) consists of individual sense organs called neuromasts, composed of hair cells.…”

Section: Introductionmentioning

confidence: 99%

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Pituitary adenylate cyclase–activating polypeptide (PACAP-38) plays an inhibitory role against inflammation induced by chemical damage to zebrafish hair cells

2018

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Pituitary adenylate cyclase–activating polypeptide (PACAP-38) is a common neuropeptide exerting a wide spectrum of functions in many fields, including immunology. In the present study, 5-day post-fertilization (dpf) zebrafish larvae of three diverse genetic lines [transgenic lines Tg(MPX:GFP) with GFP-labelled neutrophils and Tg(pou4f3:GAP-GFP) with GFP-labelled hair cells and the wild-type Tuebingen] were used to investigate an inhibitory role of PACAP-38 in inflammation associated with damaged hair cells of the lateral line. Individuals of each genetic line were assigned to four groups: (1) control, and those consisting of larvae exposed to (2) 10 µM CuSO4, (3) 10 µM CuSO4+100 nM PACAP-38 and (4) 100 nM PACAP-38, respectively. Forty-minute exposure to CuSO4 solution was applied to evoke necrosis of hair cells and consequent inflammation. The inhibitory role of PACAP-38 was investigated in vivo under a confocal microscope by counting neutrophils migrating towards damaged hair cells in Tg(MPX:GFP) larvae. In CuSO4-treated individuals, the number of neutrophils associated with hair cells was dramatically increased, while PACAP-38 co-treatment resulted in its over 2-fold decrease. However, co-treatment with PACAP-38 did not prevent hair cells from extensive necrosis, which was found in Tg(pou4f3:GAP-GFP) individuals. Real-Time PCR analysis performed in wild-type larvae demonstrated differential expression pattern of stress and inflammation inducible markers. The most significant findings showed that CuSO4 exposure up-regulated the expression of IL-8, IL-1β, IL-6 and ATF3, while after PACAP-38 co-treatment expression levels of these genes were significantly decreased. The presence of transcripts for all PACAP receptors in neutrophils was also revealed. Adcyap1r1a and vipr1b appeared to be predominant forms. The present results suggest that PACAP-38 should be considered as a factor playing an important regulatory role in inflammatory response associated with pathological processes affecting zebrafish hair cells and it cannot be excluded that this interesting property has more universal significance.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pituitary adenylate cyclase–activating polypeptide (PACAP-38) plays an inhibitory role against inflammation induced by chemical damage to zebrafish hair cells

2018

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“…PACAP is now considered to be a potent neuroprotective and cytoprotective peptide with potential therapeutic use in numerous diseases [7][8][9][10][11][12][13]. The neuroprotective effects of PACAP have been shown in several different cell types in vitro against various toxic agents, such as oxidative stress, glutamate or 6-hydroxydopamine [14][15][16]. In vivo descriptions have also proven that PACAP is protective in global and focal cerebral ischemia [15,17,18], traumatic brain injury and neurodegenerative diseases [19,20].…”

Section: Text: Introductionmentioning

confidence: 99%

Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration

Vaczy

Kovari

Kovács

et al. 2018

CPD

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Purpose. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective peptide that has been shown to exert protective effects in different models of neurodegenerative diseases, including retinal degenerations. Data obtained from PACAPdeficient (PACAP KO) mice provide evidence that endogenous PACAP has neuroprotective role in different pathologies. PACAP KO mice show enhanced sensitivity to different insults, such as oxidative stress, hypoxia and inflammation. The aim of the present study was to investigate the protective effects of endogenous PACAP in retinal inflammation. Methods. Endotoxin-caused eye inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS) in PACAP KO and wild type (Wt) mice. After LPS treatment, retinas were processed for histological examination. To detect the alterations of different proteins and cytokines, immunohistochemical, western blot and cytokine array were used. We also performed dark-adapted electroretinography (ERG) to detect the functional differences. Results. The thickness of nearly all layers was significantly less in LPS-injected PACAP KO mice compared to Wt animals. Increased expression of glial fibrillary acidic protein (GFAP) was induced in Müller glial cells after LPS treatment, which was more intense in PACAP KO mice. The levels of pAkt and pGSK were decreased in PACAP KO group during inflammation. LPS treatment significantly increased cytokines (sICAM-1, JE, TIMP-1) in both treated groups, but it was more expressed in PACAP KO animals. Furthermore, ERG responses were disturbed after LPS injection in PACAP KO mice. Conclusion. Our results showed that endogenous PACAP has a protective role in LPS-caused retinal inflammation.

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“…These approaches can provide a range of information from a general understanding of the physiological function of a neuropeptide to judging whether neuropeptides are therapeutically active (Wickström et al, 2004;Zhang et al, 2016). Neuropeptides, their antagonists and siRNAs can be delivered to an organism in several different ways, including by injection (Javadian et al, 2016;Narváez et al, 2016), incubation in media containing molecules (Chen et al, 2016b;Kasica et al, 2016) and even microdialysis (Torregrossa and Kalivas, 2008). siRNAs, RNA molecules that interfere with an expression of a gene, may require more sophisticated methods of delivery (e.g.…”

Section: Altering Neuropeptide Contentmentioning

confidence: 99%

New techniques, applications and perspectives in neuropeptide research

DeLaney

Buchberger

Atkinson

et al. 2018

Journal of Experimental Biology

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Neuropeptides are one of the most diverse classes of signaling molecules and have attracted great interest over the years owing to their roles in regulation of a wide range of physiological processes. However, there are unique challenges associated with neuropeptide studies stemming from the highly variable molecular sizes of the peptides, low concentrations, high degree of structural diversity and large number of isoforms. As a result, much effort has been focused on developing new techniques for studying neuropeptides, as well as novel applications directed towards learning more about these endogenous peptides. The areas of importance for neuropeptide studies include structure, localization within tissues, interaction with their receptors, including ion channels, and physiological function. Here, we discuss these aspects and the associated techniques, focusing on technologies that have demonstrated potential in advancing the field in recent years. Most identification and structural information has been gained by mass spectrometry, either alone or with confirmations from other techniques, such as nuclear magnetic resonance spectroscopy and other spectroscopic tools. While mass spectrometry and bioinformatic tools have proven to be the most powerful for large-scale analyses, they still rely heavily on complementary methods for confirmation. Localization within tissues, for example, can be probed by mass spectrometry imaging, immunohistochemistry and radioimmunoassays. Functional information has been gained primarily from behavioral studies coupled with tissue-specific assays, electrophysiology, mass spectrometry and optogenetic tools. Concerning the receptors for neuropeptides, the discovery of ion channels that are directly gated by neuropeptides opens up the possibility of developing a new generation of tools for neuroscience, which could be used to monitor neuropeptide release or to specifically change the membrane potential of neurons. It is expected that future neuropeptide research will involve the integration of complementary bioanalytical technologies and functional assays.

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Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Against Oxidative Stress in Zebrafish Hair Cells

Cited by 14 publications

References 96 publications

Pituitary adenylate cyclase–activating polypeptide (PACAP-38) plays an inhibitory role against inflammation induced by chemical damage to zebrafish hair cells

Pituitary adenylate cyclase–activating polypeptide (PACAP-38) plays an inhibitory role against inflammation induced by chemical damage to zebrafish hair cells

Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration

New techniques, applications and perspectives in neuropeptide research

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