Dépôt numérique

Intracrine pharmacology of pituitary adenylate cyclase-activating polypeptide

Doan, Ngoc Duc; Nguyen, Thi Tuyet Mai; Létourneau, Myriam; Vaudry, David; Vaudry, Hubert; Chatenet, David ORCID logoORCID: 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.

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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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