Unusual behavior of pituitary adenylate cyclase activating polypeptide (PACAP) on survival, signal transduction and receptorial binding in human trophoblast cells
Gabriella
Horváth1*,
Boglarka
Racz2,
Andrea
Tamas1,
Peter
Kiss1,
Reka
Brubel1,
Arpad
Boronkai2,
Andrea
Lubics1,
Jozsef
Nemeth3,
Gabor
Toth4,
Tamas
Varga5,
Donat
Szogyi1,
Eszter
Fonagy1,
József
Farkas1,
Aliz
Barakonyi6,
Laszlo
Szereday6,
Miklos
Koppan1, 5 and
Dóra
Reglődi1
-
1
Department of Anatomy, University of Pecs, Departments of Anatomy, Hungary
-
2
Departments of Biochemistry and Medical Chemistry, University of Pecs, Hungary
-
3
University of Debrecen, Department of Pharmacology and Pharmacotherapy, Hungary
-
4
University of Szeged, Department of Medical Chemistry, Hungary
-
5
Department of Obstetrics and Gynecology , University of Pecs, Hungary
-
6
Medical Microbiology and Immunology,University of Pecs, Hungary
PACAP is present in the nervous system and in peripheral organs, including the placenta. It occurs in two forms: PACAP1-38 and PACAP1-27. PACAP is generally known as a survival-promoting peptide acting mainly on MAPK signaling pathways. Little is known about its distribution, functions, and effects on the survival and signaling mechanisms of human trophoblast cells. The first aim of the present study was to determine the concentration of PACAP1-38 and PACAP1-27 in human first trimester and full-term placentas. The second aim was to investigate the effect of PACAP on cell survival and on the components of signaling pathways in choriocarcinoma cells exposed to different toxic agents. We examined the effects of PACAP1-38 and PACAP6-38 on the phosphorylation of p38MAPK, ERK1/2 and JNK in trophoblast cells. We found that PACAP1-38 occurs at much higher concentrations than PACAP1-27, and they show changes during pregnancy. Investigating the effects of PACAP on trophoblast cells treated with various toxic agents, we observed that, in contrast to other cell types, PACAP potentiated the survival-decreasing effects of oxidative stress and chemically induced hypoxia. In addition, PACAP1-38 changes induced by H2O2 in signaling pathways were further expressed after PACAP treatment. PACAP6-38 is generally used as an antagonist to PAC1/VPAC1 receptors. However, in our present study PACAP6-38 clearly behaved as an agonist on human cytotrophoblast cells. In summary, PACAP shows an unusual behavior in trophoblast cells: it sensitizes the cells to some stressors and PACAP6-38 behaves as an agonist, which may represent a novel tissue- or target cell-dependent effect of PACAP.
Conference:
12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009.
Presentation Type:
Poster Presentation
Topic:
Homeostatic regulatory mechanisms
Citation:
Horváth
G,
Racz
B,
Tamas
A,
Kiss
P,
Brubel
R,
Boronkai
A,
Lubics
A,
Nemeth
J,
Toth
G,
Varga
T,
Szogyi
D,
Fonagy
E,
Farkas
J,
Barakonyi
A,
Szereday
L,
Koppan
M and
Reglődi
D
(2009). Unusual behavior of pituitary adenylate cyclase activating polypeptide (PACAP) on survival, signal transduction and receptorial binding in human trophoblast cells.
Front. Syst. Neurosci.
Conference Abstract:
12th Meeting of the Hungarian Neuroscience Society.
doi: 10.3389/conf.neuro.01.2009.04.012
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Received:
25 Feb 2009;
Published Online:
25 Feb 2009.
*
Correspondence:
Gabriella Horváth, Department of Anatomy, University of Pecs, Departments of Anatomy, Pecs, Hungary, gabriella.horvath@aok.pte.hu