NDA@SZTAKI

Effects of pituitary adenylate cyclase activating polypeptide on small intestinal INT 407 cells

Illés, Anita

Opper, Balázs

Reglődi, Dóra

Kerényi, Mónika

Czétány, Péter

Boronkai, �rpad

Schäfer, Eszter

Tóth, Gábor

Fábián, Eszter

Horváth, Gabriella

Elsevier

2017

R850-854 Experimental medicine / kisérleti orvostudomány

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide having a widespread
distribution both in the nervous system and peripheral organs including the gastrointestinal tract. It has been
shown to exert actions on intestinal functions, mainly affecting glandular secretion and motility. PACAP has several
different effects on cell survival depending on the cell type and the applied stimulus. Its influences on small
intestinal epithelial cells are not yet elucidated, therefore the aim of the present study was to investigate the
effects of PACAP on intestinal epithelial cells having high turnover (INT 407) against different harmful stimuli,
such as oxidative stress, in vitro hypoxia and gamma radiation. We tested the effect of PACAP on proliferation
and cell survival using MTT assay. Moreover, various cancer-related factors were evaluated by oncology array.
PACAP did not influence the proliferation rate of INT 407 cells. Its cell survival-enhancing effect could be detected
against oxidative stress, but not against in vitro hypoxia or gamma irradiation. Clonogenic survival assay
was performed to analyze the effect of PACAP on clonogenic potential of cells exposed to gamma radiation. Surprisingly,
PACAP enhanced the clone-forming ability decrease induced by irradiation. Western blot analysis of
ERK1/2 phosphorylation was performed in order to obtain further information on the molecular background.
Our data showed phospho-ERK1/2 suppression of PACAP in irradiated cells. Furthermore, the role of endogenous
PACAP against oxidative stress was also investigated performing ADCYAP1 small interfering RNA transfection.
We found significant difference in the cell vulnerability between cells undergoing silencing and cells without
transfection suggesting the protective role of the endogenously present PACAP against oxidative stress in INT
407 cells. In summary, PACAP seems to be able to exert contradictory effects in INT 407 cells depending on the
applied stressor, suggesting its regulatory role in the cellular household.

magyar

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/62577/1/Illesetal_proof_NPEP.pdf

Illés, Anita and Opper, Balázs and Reglődi, Dóra and Kerényi, Mónika and Czétány, Péter and Boronkai, �rpad and Schäfer, Eszter and Tóth, Gábor and Fábián, Eszter and Horváth, Gabriella (2017) Effects of pituitary adenylate cyclase activating polypeptide on small intestinal INT 407 cells. NEUROPEPTIDES. ISSN 0143-4179 (In Press)

http://real.mtak.hu/62577/

https://doi.org/10.1016/j.npep.2017.07.002

doi: 10.1016/j.npep.2017.07.002.