Doan, Ngoc Duc; Nguyen, Thi Tuyet Mai; Létourneau, Myriam; Vaudry, David; Vaudry, Hubert; Chatenet, David 
ORCID: https://orcid.org/0000-0002-7270-4328 et Fournier, Alain
(2012).
Intracrine pharmacology of pituitary adenylate cyclase-activating polypeptide
In: 10th International Symposium on VIP-PACAP and Related Peptides, December 13-16, 2011, Eilat, ISRAEL.
Résumé
The Pituitary Adenylate-Cyclase Activating Polypeptide
(PACAP), a hypophysiotropic neurohormone initially isolated from ovine hypothalamic extracts, participates in the
regulation of pleiotropic actions including control of tumor
cell proliferation, inflammation, and apoptosis. The recent
discovery of nuclear PACAP receptors in the testis as well
as the physico-chemical characteristics of PACAP, i.e.
extended α-helix exhibiting basic residues, prompted us to
evaluate the propensity of PACAP to cross the plasma
membrane. Using confocal microscopy and FACS analysis,
we demonstrated the ability of FITC-conjugated PACAP to
efficiently penetrate into the internal compartment in a
receptor-independent pathway. Mechanistic studies revealed
that PACAP translocated into cells by multiple mechanisms
including direct translocation and endocytosis through
clathrin-coated pits. Using binding and calcium assays
along with photolabeling experiments and transcription
initiation assay on rat nuclear fractions from various tissues
including brain, testis, spleen, kidney and adrenal gland, we
identified functional nuclear binding sites for PACAP.
Finally, we demonstrated the ability of biotinylated PACAP
to efficiently deliver large molecule such as streptavidin into
cells, enabling the development of PACAP-based cell
penetrating peptide. These findings contribute to the
characterization of PACAP as an intracrine factor and
extend the scope of the usefulness of PACAP derivatives
for therapeutic purposes.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Informations complémentaires: | Affiche scientifique Journal of Molecular Neuroscience 48(suppl. 1):S161 |
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 28 janv. 2024 14:55 |
| Dernière modification: | 28 janv. 2024 14:55 |
| URI: | https://espace.inrs.ca/id/eprint/14121 |
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