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Effects of PACAP on Oxidative Stress-Induced Cell Death in Rat Kidney and Human Hepatocyte Cells

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Abstract

Oxidative stress plays an important role in various renal and hepatic pathologies, and reduction of oxidative stress-induced processes is an important protective strategy in tissues of diverse origins against harmful stimuli. Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-known cytotrophic and cytoprotective peptide. PACAP promotes cell survival in numerous cells and tissues exposed to various stimuli. Protective effects of PACAP have been shown in the kidney, but it is not known whether PACAP is protective against oxidative stress in renal cells. Little is known about the effects of PACAP in the liver. The aim of the present study was to investigate whether PACAP is protective against oxidative stress in primary rat kidney cell culture and whether PACAP has any effect on cell survival in human WRL-68 hepatocytes and HEP-G2 hepatocellular carcinoma cells subjected to oxidative stress. Cells were exposed to various concentrations of H2O2 with or without PACAP co-treatment and cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test (MTT). We found that oxidative stress induced a significant decrease in cell viability in both cell lines. PACAP could dose-dependently increase the percentage of living cells in kidney cells, but it failed to do so in hepatocytes. Given the survival-promoting effects of PACAP against oxidative stress in rat kidney, we conducted a further experiment to determine whether PACAP influences the markers of oxidative stress in vivo. We have proven earlier that PACAP was effective in kidney ischemia/reperfusion injury in vivo. In the present study, we determined the levels of the oxidative stress marker malondialdehyde and the activity of the scavenger molecules glutathione (GSH) and superoxide dismutase (SOD) following kidney ischemia/reperfusion in rats. We found that PACAP significantly increased the level of GSH and counteracted the marked reduction of SOD activity after ischemia/reperfusion in vivo. In summary, the present study showed that while PACAP was able to significantly increase the cell survival in primary kidney cell cultures exposed to oxidative stress, possibly involving interaction with the endogenous scavenger system, it failed to influence the viability of normal or cancerous hepatocytes.

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Acknowledgments

This work was supported by the following grants: OTKA K72592, F67830, CNK 78480, PD77474, Bolyai Scholarship, ETT278-04/2009, University of Pécs Medical School Research Grant 2009, and Richter Gedeon Foundation.

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Authors and Affiliations

  1. Department of Anatomy, University of Pécs, Szigeti u 12, 7624, Pécs, Hungary

    Gabriella Horvath, Reka Brubel, Dora Reglodi, Balazs Opper, Eszter Laszlo, Lidia Hau, Peter Kiss & Andrea Tamas

  2. Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary

    Krisztina Kovacs & Boglarka Racz

  3. Department of Surgical Research and Techniques, University of Pécs, Pécs, Hungary

    Andrea Ferencz

  4. Department of Surgery, University of Pécs, Pécs, Hungary

    Peter Szakaly

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  1. Gabriella Horvath
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  2. Reka Brubel
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  5. Balazs Opper
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  12. Boglarka Racz
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Correspondence to Gabriella Horvath.

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Horvath, G., Brubel, R., Kovacs, K. et al. Effects of PACAP on Oxidative Stress-Induced Cell Death in Rat Kidney and Human Hepatocyte Cells. J Mol Neurosci 43, 67–75 (2011). https://doi.org/10.1007/s12031-010-9428-8

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  • DOI: https://doi.org/10.1007/s12031-010-9428-8

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