Neurotoxicity Research

, Volume 26, Issue 3, pp 230–239

PACAP Protects Against Inflammatory-Mediated Toxicity in Dopaminergic SH-SY5Y Cells: Implication for Parkinson’s Disease

  • Dwayne Brown
  • Andrea Tamas
  • Dora Reglodi
  • Yousef Tizabi
Original Article

Abstract

There has been a growing recognition of the role of neuroinflammation caused by microglia-exaggerated release of inflammatory mediators in the pathogenesis of Parkinson’s disease (PD). Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous 38 amino acid containing neuropeptide that has been shown to possess neurotrophic as well as neuroprotective properties. In this study, we sought to determine whether PACAP could protect SH-SY5Y dopaminergic cells against toxicity induced by inflammatory mediators. For this purpose, THP-1 cells which possess microglia-like property were stimulated by a combination of lipopolysaccharide (LPS) and interferon gamma (IFN-γ), and the media containing inflammatory mediators were isolated and applied to SH-SY5Y cells. Such treatment resulted in approximately 54 % cell death as well as a reduction in brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-binding protein (p-CREB). Pretreatment of the SH-SY5Y cells with PACAP (1-38) dose-dependently attenuated toxicity induced by the inflammatory mediators. PACAP effects, in turn, were dose-dependently blocked by the PACAP receptor antagonist (PACAP 6-38). These results suggest protective effects of PACAP against inflammatory-induced toxicity in a cellular model of PD that is likely mediated by enhancement of cell survival markers through activation of PACAP receptors. Hence, PACAP or its agonists could be of therapeutic benefit in inflammatory-mediated PD.

Keywords

PACAP Inflammation SH-SY5Y cell line Neuroprotection Neurotrophic factors Apoptosis Parkinson’s disease 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Dwayne Brown
    • 1
  • Andrea Tamas
    • 2
  • Dora Reglodi
    • 2
  • Yousef Tizabi
    • 1
  1. 1.Department of PharmacologyHoward University College of MedicineWashingtonUSA
  2. 2.Department of Anatomy, PTE-MTA “Lendulet” PACAP Research TeamUniversity of PecsPecsHungary

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