Mice deficient in pituitary adenylate cyclase activating polypeptide display increased sensitivity to renal oxidative stress in vitro

Gabriella Horvath, L. Márk, Reka Brubel, Peter Szakaly, B. Rácz, P. Kiss, A. Tamás, Z. Helyes, A. Lubics, Hitoshi Hashimoto, Akemichi Baba, Norihito Shintani, Gergely Furjes, J. Németh, D. Reglodi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, showing widespread occurrence in the nervous system and also in peripheral organs. The neuroprotective effects of PACAP are well-established in different neuronal systems against noxious stimuli in vitro and in vivo. Recently, its general cytoprotective actions have been recognized, including renoprotective effects. However, the effect of endogenous PACAP in the kidneys is not known. The main aim of the present study was to investigate whether the lack of this endogenous neuropeptide influences survival of kidney cells against oxidative stress. First, we determined the presence of endogenous PACAP from mouse kidney homogenates by mass spectrometry and PACAP-like immunoreactivity by radioimmunoassay. Second, primary cultures were isolated from wild type and PACAP deficient mice and cell viability was assessed following oxidative stress induced by 0.5, 1.5 and 3 mM H2O2. Our mass spectrometry and radioimmunoassay results show that PACAP is endogenously present in the kidney. The main part of our study revealed that the sensitivity of cells from PACAP deficient mice was increased to oxidative stress: both after 2 or 4 h of exposure, cell viability was significantly reduced compared to that from control wild type mice. This increased sensitivity of kidneys from PACAP deficient mice could be counteracted by exogenously given PACAP38. These results show, for the first time, that endogenous PACAP protects against oxidative stress in the kidney, and that PACAP may act as a stress sensor in renal cells. These findings further support the general cytoprotective nature of this neuropeptide.

Original languageEnglish
Pages (from-to)70-74
Number of pages5
JournalNeuroscience Letters
Volume469
Issue number1
DOIs
Publication statusPublished - Jan 18 2010

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Pituitary Adenylate Cyclase-Activating Polypeptide
Oxidative Stress
Kidney
Neuropeptides
Cell Survival
Radioimmunoassay
In Vitro Techniques
Mass Spectrometry
Neuroprotective Agents
Nervous System

Keywords

  • Cell viability
  • Oxidative stress
  • PACAP knockout mice
  • Renoprotection

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mice deficient in pituitary adenylate cyclase activating polypeptide display increased sensitivity to renal oxidative stress in vitro. / Horvath, Gabriella; Márk, L.; Brubel, Reka; Szakaly, Peter; Rácz, B.; Kiss, P.; Tamás, A.; Helyes, Z.; Lubics, A.; Hashimoto, Hitoshi; Baba, Akemichi; Shintani, Norihito; Furjes, Gergely; Németh, J.; Reglodi, D.

In: Neuroscience Letters, Vol. 469, No. 1, 18.01.2010, p. 70-74.

Research output: Contribution to journalArticle

Horvath, Gabriella ; Márk, L. ; Brubel, Reka ; Szakaly, Peter ; Rácz, B. ; Kiss, P. ; Tamás, A. ; Helyes, Z. ; Lubics, A. ; Hashimoto, Hitoshi ; Baba, Akemichi ; Shintani, Norihito ; Furjes, Gergely ; Németh, J. ; Reglodi, D. / Mice deficient in pituitary adenylate cyclase activating polypeptide display increased sensitivity to renal oxidative stress in vitro. In: Neuroscience Letters. 2010 ; Vol. 469, No. 1. pp. 70-74.
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AU - Horvath, Gabriella

AU - Márk, L.

AU - Brubel, Reka

AU - Szakaly, Peter

AU - Rácz, B.

AU - Kiss, P.

AU - Tamás, A.

AU - Helyes, Z.

AU - Lubics, A.

AU - Hashimoto, Hitoshi

AU - Baba, Akemichi

AU - Shintani, Norihito

AU - Furjes, Gergely

AU - Németh, J.

AU - Reglodi, D.

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N2 - Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, showing widespread occurrence in the nervous system and also in peripheral organs. The neuroprotective effects of PACAP are well-established in different neuronal systems against noxious stimuli in vitro and in vivo. Recently, its general cytoprotective actions have been recognized, including renoprotective effects. However, the effect of endogenous PACAP in the kidneys is not known. The main aim of the present study was to investigate whether the lack of this endogenous neuropeptide influences survival of kidney cells against oxidative stress. First, we determined the presence of endogenous PACAP from mouse kidney homogenates by mass spectrometry and PACAP-like immunoreactivity by radioimmunoassay. Second, primary cultures were isolated from wild type and PACAP deficient mice and cell viability was assessed following oxidative stress induced by 0.5, 1.5 and 3 mM H2O2. Our mass spectrometry and radioimmunoassay results show that PACAP is endogenously present in the kidney. The main part of our study revealed that the sensitivity of cells from PACAP deficient mice was increased to oxidative stress: both after 2 or 4 h of exposure, cell viability was significantly reduced compared to that from control wild type mice. This increased sensitivity of kidneys from PACAP deficient mice could be counteracted by exogenously given PACAP38. These results show, for the first time, that endogenous PACAP protects against oxidative stress in the kidney, and that PACAP may act as a stress sensor in renal cells. These findings further support the general cytoprotective nature of this neuropeptide.

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