PMID- 35216232
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20220314
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 4
DP  - 2022 Feb 14
TI  - PACAP-38 Induces Transcriptomic Changes in Rat Trigeminal Ganglion Cells Related 
      to Neuroinflammation and Altered Mitochondrial Function Presumably via PAC1/VPAC2 
      Receptor-Independent Mechanism.
LID - 10.3390/ijms23042120 [doi]
LID - 2120
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a broadly expressed 
      neuropeptide which has diverse effects in both the peripheral and central nervous 
      systems. While its neuroprotective effects have been shown in a variety of 
      disease models, both animal and human data support the role of PACAP in migraine 
      generation. Both PACAP and its truncated derivative PACAP(6-38) increased calcium 
      influx in rat trigeminal ganglia (TG) primary sensory neurons in most 
      experimental settings. PACAP(6-38), however, has been described as an antagonist 
      for PACAP type I (known as PAC1), and Vasoactive Intestinal Polypeptide Receptor 
      2 (also known as VPAC2) receptors. Here, we aimed to compare the signaling 
      pathways induced by the two peptides using transcriptomic analysis. Rat 
      trigeminal ganglion cell cultures were incubated with 1 microM PACAP-38 or 
      PACAP(6-38). Six hours later RNA was isolated, next-generation RNA sequencing was 
      performed and transcriptomic changes were analyzed to identify differentially 
      expressed genes. Functional analysis was performed for gene annotation using the 
      Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome 
      databases. We found 200 common differentially expressed (DE) genes for these two 
      neuropeptides. Both PACAP-38 and PACAP(6-38) treatments caused significant 
      downregulation of NADH: ubiquinone oxidoreductase subunit B6 and upregulation of 
      transient receptor potential cation channel, subfamily M, member 8. The common 
      signaling pathways induced by both peptides indicate that they act on the same 
      target, suggesting that PACAP activates trigeminal primary sensory neurons via a 
      mechanism independent of the identified and cloned PAC1/VPAC2 receptor, either 
      via another target structure or a different splice variant of PAC1/VPAC2 
      receptors. Identification of the target could help to understand key mechanisms 
      of migraine.
FAU - Takacs-Lovasz, Krisztina
AU  - Takacs-Lovasz K
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
FAU - Kun, Jozsef
AU  - Kun J
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Aczel, Timea
AU  - Aczel T
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
FAU - Urban, Peter
AU  - Urban P
AUID- ORCID: 0000-0003-4043-3428
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Gyenesei, Attila
AU  - Gyenesei A
AD  - Szentagothai Research Centre, Bioinformatics Research Group, Genomics and 
      Bioinformatics Core Facility, University of Pecs, H-7624 Pecs, Hungary.
FAU - Bolcskei, Kata
AU  - Bolcskei K
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
FAU - Szoke, Eva
AU  - Szoke E
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
FAU - Helyes, Zsuzsanna
AU  - Helyes Z
AD  - Department of Pharmacology and Pharmacotherapy, Medical School & Szentagothai 
      Research Centre, Molecular Pharmacology Research Group, Centre for Neuroscience, 
      University of Pecs, H-7624 Pecs, Hungary.
LA  - eng
GR  - 2017-1.2.1-NKP-2017-00002 (NAP-2; Chronic Pain Research Group)/National Brain 
      Research Program/
GR  - (GINOP)-2.3.2-15-2016-00050 (Peptidergic Signaling in Health and Disease; 
      PEPSYS)/Economy Development and Innovation Operative Programme/
GR  - GINOP 2.3.2-15-2016-0034/Economy Development and Innovation Operative Programme/
GR  - (EFOP) 3.6.2-16-2017-00008 (2017-2019)/Human Resource Operative Programme/
GR  - EFOP-3.6.1-16-2016-00004/Human Resource Operative Programme/
GR  - OTKA FK132587/National Research Development and Innovation Office/
GR  - GINOP-2.3.4-15-2020-00010/Economy Development and Innovation Operative Programme/
GR  - GINOP-2.3.1-20-2020-00001/Economy Development and Innovation Operative Programme/
GR  - BECOMING, 2019-1-HU01-KA203-061251/Educating Experts of the Future: Developing 
      Bioinformatics and Biostatistics competencies of European Biomedical Students/
GR  - TKP2020-IKA-08/National Research, Development and Innovation Fund of Hungary/
PT  - Journal Article
DEP - 20220214
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I)
RN  - 0 (Receptors, Vasoactive Intestinal Peptide, Type II)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Migraine Disorders/genetics/metabolism
MH  - Mitochondria/*drug effects/genetics
MH  - Neuroinflammatory Diseases/*drug therapy/genetics
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/*genetics
MH  - Receptors, Vasoactive Intestinal Peptide, Type II/*genetics
MH  - Signal Transduction/drug effects/genetics
MH  - Transcriptome/*drug effects/genetics
MH  - Trigeminal Ganglion/*drug effects
PMC - PMC8874739
OTO - NOTNLM
OT  - intracellular calcium
OT  - mitochondrial electron transport chain
OT  - pituitary adenylated cyclase-activating polypeptide (PACAP)
OT  - transcriptomics
OT  - trigeminal ganglion
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/02/27 06:00
MHDA- 2022/03/15 06:00
PMCR- 2022/02/14
CRDT- 2022/02/26 01:07
PHST- 2022/01/13 00:00 [received]
PHST- 2022/02/07 00:00 [revised]
PHST- 2022/02/09 00:00 [accepted]
PHST- 2022/02/26 01:07 [entrez]
PHST- 2022/02/27 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2022/02/14 00:00 [pmc-release]
AID - ijms23042120 [pii]
AID - ijms-23-02120 [pii]
AID - 10.3390/ijms23042120 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Feb 14;23(4):2120. doi: 10.3390/ijms23042120.