PMID- 24740430
OWN - NLM
STAT- MEDLINE
DCOM- 20151013
LR  - 20211021
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 26
IP  - 3
DP  - 2014 Oct
TI  - PACAP protects against inflammatory-mediated toxicity in dopaminergic SH-SY5Y 
      cells: implication for Parkinson's disease.
PG  - 230-9
LID - 10.1007/s12640-014-9468-x [doi]
AB  - 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-gamma), 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.
FAU - Brown, Dwayne
AU  - Brown D
AD  - Department of Pharmacology, Howard University College of Medicine, 520 W Street 
      NW, Washington, DC, 20059, USA.
FAU - Tamas, Andrea
AU  - Tamas A
FAU - Reglodi, Dora
AU  - Reglodi D
FAU - Tizabi, Yousef
AU  - Tizabi Y
LA  - eng
GR  - 2 SO6 GM08016-39/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140417
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (ADCYAP1 protein, human)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (pituitary adenylate-cyclase-activating-peptide (6-38))
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dopaminergic Neurons/drug effects/*physiology
MH  - Encephalitis/*metabolism
MH  - Humans
MH  - Interferon-gamma/immunology
MH  - Lipopolysaccharides/immunology
MH  - Parkinson Disease/*physiopathology
MH  - Peptide Fragments/pharmacology
MH  - Phosphorylation
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology/*physiology
EDAT- 2014/04/18 06:00
MHDA- 2015/10/16 06:00
CRDT- 2014/04/18 06:00
PHST- 2014/01/21 00:00 [received]
PHST- 2014/04/01 00:00 [accepted]
PHST- 2014/03/21 00:00 [revised]
PHST- 2014/04/18 06:00 [entrez]
PHST- 2014/04/18 06:00 [pubmed]
PHST- 2015/10/16 06:00 [medline]
AID - 10.1007/s12640-014-9468-x [doi]
PST - ppublish
SO  - Neurotox Res. 2014 Oct;26(3):230-9. doi: 10.1007/s12640-014-9468-x. Epub 2014 Apr 
      17.