Distribution and Molecular Evolution of the Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its Receptors in the Lizard Podarcis sicula (Squamata, Lacertidae)

Valiante, Salvatore; Prisco, Marina; Falco, Maria De; Sellitti, Anna; Zambrano, Immacolata; Sciarrillo, Rosaria; Capaldo, Anna; Andreuccetti, Piero; Laforgia, Vincenza

doi:10.1007/s12031-009-9178-7

Cited by 8 publications

(5 citation statements)

References 44 publications

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“…In reptiles, few members of this family have been reported to date. A VIP and GCG peptides were isolated from the Alligator mississippiensis , the nucleotide precursor of the latter peptide reported from the Heloderma suspectum [ 28 - 30 ] and a PRP/PACAP mRNA was recently characterised from the Italian wall lizard Podarcis sicula [ 31 , 32 ]. Sequence database searches on the lizard Anolis carolinensis genome identified for the first time the genes encoding the reptile PHI/VIP (ENSACAG00000005619), PRP/PACAP (ENSACAG00000008729), GHRH (ENSACAG00000011836), GCG/GLP (ENSACAG00000014182) and GIP (ENSACAG00000006291) (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

The serendipitous origin of chordate secretin peptide family members

et al. 2010

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BackgroundThe secretin family is a pleotropic group of brain-gut peptides with affinity for class 2 G-protein coupled receptors (secretin family GPCRs) proposed to have emerged early in the metazoan radiation via gene or genome duplications. In human, 10 members exist and sequence and functional homologues and ligand-receptor pairs have been characterised in representatives of most vertebrate classes. Secretin-like family GPCR homologues have also been isolated in non-vertebrate genomes however their corresponding ligands have not been convincingly identified and their evolution remains enigmatic.ResultsIn silico sequence comparisons failed to retrieve a non-vertebrate (porifera, cnidaria, protostome and early deuterostome) secretin family homologue. In contrast, secretin family members were identified in lamprey, several teleosts and tetrapods and comparative studies revealed that sequence and structure is in general maintained. Sequence comparisons and phylogenetic analysis revealed that PACAP, VIP and GCG are the most highly conserved members and two major peptide subfamilies exist; i) PACAP-like which includes PACAP, PRP, VIP, PH, GHRH, SCT and ii) GCG-like which includes GCG, GLP1, GLP2 and GIP. Conserved regions flanking secretin family members were established by comparative analysis of the Takifugu, Xenopus, chicken and human genomes and gene homologues were identified in nematode, Drosophila and Ciona genomes but no gene linkage occurred. However, in Drosophila and nematode genes which flank vertebrate secretin family members were identified in the same chromosome.ConclusionsReceptors of the secretin-like family GPCRs are present in protostomes but no sequence homologues of the vertebrate cognate ligands have been identified. It has not been possible to determine when the ligands evolved but it seems likely that it was after the protostome-deuterostome divergence from an exon that was part of an existing gene or gene fragment by rounds of gene/genome duplication. The duplicate exon under different evolutionary pressures originated the chordate PACAP-like and GCG-like subfamily groups. This event occurred after the emergence of the metazoan secretin GPCRs and led to the establishment of novel peptide-receptor interactions that contributed to the generation of novel physiological functions in the chordate lineage.

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Section: Resultsmentioning

confidence: 99%

The serendipitous origin of chordate secretin peptide family members

et al. 2010

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“…Although PACAP had greater potency than VIP to stimulate cAMP, the two peptides did not have additive effects when applied simultaneously, suggesting that they act on the same receptors (Guijarro et al 1995). Less studies have shown the presence of the peptide itself in the liver: PACAP and its mRNA are present in the liver of the lizard Podarcis sicula (Valiante et al 2009) and PACAP immunoreactivity has been found in the liver of the developing zebrafish (Mathieu et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Effects of PACAP on Oxidative Stress-Induced Cell Death in Rat Kidney and Human Hepatocyte Cells

et al. 2010

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Oxidative stress plays an important role in various renal and hepatic pathologies, and reduction of oxidative stress-induced processes is an important protective strategy in tissues of diverse origins against harmful stimuli. Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-known cytotrophic and cytoprotective peptide. PACAP promotes cell survival in numerous cells and tissues exposed to various stimuli. Protective effects of PACAP have been shown in the kidney, but it is not known whether PACAP is protective against oxidative stress in renal cells. Little is known about the effects of PACAP in the liver. The aim of the present study was to investigate whether PACAP is protective against oxidative stress in primary rat kidney cell culture and whether PACAP has any effect on cell survival in human WRL-68 hepatocytes and HEP-G2 hepatocellular carcinoma cells subjected to oxidative stress. Cells were exposed to various concentrations of H(2)O(2) with or without PACAP co-treatment and cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test (MTT). We found that oxidative stress induced a significant decrease in cell viability in both cell lines. PACAP could dose-dependently increase the percentage of living cells in kidney cells, but it failed to do so in hepatocytes. Given the survival-promoting effects of PACAP against oxidative stress in rat kidney, we conducted a further experiment to determine whether PACAP influences the markers of oxidative stress in vivo. We have proven earlier that PACAP was effective in kidney ischemia/reperfusion injury in vivo. In the present study, we determined the levels of the oxidative stress marker malondialdehyde and the activity of the scavenger molecules glutathione (GSH) and superoxide dismutase (SOD) following kidney ischemia/reperfusion in rats. We found that PACAP significantly increased the level of GSH and counteracted the marked reduction of SOD activity after ischemia/reperfusion in vivo. In summary, the present study showed that while PACAP was able to significantly increase the cell survival in primary kidney cell cultures exposed to oxidative stress, possibly involving interaction with the endogenous scavenger system, it failed to influence the viability of normal or cancerous hepatocytes.

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“…The sequence was analyzed for similarity with BLASTn program (http://www.ncbi.nlm.nih.gov/). Protein translation was done using Genamics Expression 1.1 software (Valiante et al, , ). Putative protein molecular weight was analyzed using the tools from ExPASy Molecular Biology Server (http://www.expasy.org/).…”

Section: Methodsmentioning

confidence: 99%

Molecular cloning of VIP and distribution of VIP/VPACR system in the testis ofPodarcis sicula

et al. 2014

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Using molecular, biochemical, and cytological tools, we studied the nucleotide and the deduced amino acid sequence of PHI/VIP and the distribution of VIP/VPAC receptor system in the testis of the Italian wall lizard Podarcis sicula to evaluate the involvement of such a neuropeptide in the spermatogenesis control. We demonstrated that (1) Podarcis sicula VIP had a high identity with other vertebrate VIP sequences, (2) differently from mammals, VIP was synthesized directly in the testis, and (3) VIP and its receptor VPAC2 were widely distributed in germ and somatic cells, while the VPAC1 R had a distribution limited to Leydig cells. Our results demonstrated that in Podarcis sicula the VIP sequence is highly preserved and that this neuropeptide is involved in lizard spermatogenesis and steroidogenesis.

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Distribution and Molecular Evolution of the Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its Receptors in the Lizard Podarcis sicula (Squamata, Lacertidae)

Cited by 8 publications

References 44 publications

The serendipitous origin of chordate secretin peptide family members

The serendipitous origin of chordate secretin peptide family members

Effects of PACAP on Oxidative Stress-Induced Cell Death in Rat Kidney and Human Hepatocyte Cells

Molecular cloning of VIP and distribution of VIP/VPACR system in the testis ofPodarcis sicula

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