Document Detail


VIP down-regulates the inflammatory potential and promotes survival of dying (neural crest-derived) corneal endothelial cells ex vivo: necrosis to apoptosis switch and up-regulation of Bcl-2 and N-cadherin.
MedLine Citation:
PMID:  19250342     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neuropeptide vasoactive intestinal peptide (VIP) is anti-inflammatory and protective in the immune and nervous systems, respectively. This study demonstrated in corneal endothelial (CE) cells injured by severe oxidative stress (1.4 mM H(2)O(2)) in bovine corneal organ cultures that VIP pre-treatment (0, 10(-10), 10(-8), and 10(-6) M; 15 min), in a VIP concentration-dependent manner, switched the inflammation-causing necrosis to inflammation-neutral apoptosis (showing annexin V-binding, chromatin condensation, and DNA fragmentation) and upheld ATP levels in a VIP antagonist (SN)VIPhyb-sensitive manner, while up-regulated mRNA levels of the anti-apoptotic Bcl-2 and the differentiation marker N-cadherin in a kinase A inhibitor-sensitive manner. As a result, VIP, in a concentration-dependent and VIP antagonist-sensitive manners, promoted long-term CE cell survival. ATP levels, a determining factor in the choice of apoptosis versus necrosis, measured after VIP pre-treatment and 0.5 min post-H(2)O(2) were 39.6 +/- 3.3, 50.8 +/- 6.2, 60.1 +/- 4.8, and 53.6 +/- 5.3 pmoles/microg protein (mean +/- SEM), respectively (p < 0.05, anova). VIP treatment alone concentration-dependently increased levels of N-cadherin (Koh et al. 2008), the phosphorylated cAMP-responsive-element binding protein and Bcl-2, while 10(-8) M VIP, in a VIP antagonist (SN)VIPhyb-sensitive manner, increased ATP level by 38% (p < 0.02) and decreased glycogen level by 32% (p < 0.02). VPAC1 (not VPAC2) receptor was expressed in CE cells. Thus, CE cell VIP/VPAC1 signaling is both anti-inflammatory and protective in the corneal endothelium.
Authors:
Shay-Whey M Koh; Jason Cheng; Rebecca M Dodson; Chao-Yar T Ku; Cara J Abbondandolo
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-02-24
Journal Detail:
Title:  Journal of neurochemistry     Volume:  109     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-05     Completed Date:  2009-06-09     Revised Date:  2011-10-21    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  792-806     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology & Visual Sciences, University of Maryland, Baltimore, Maryland 21201, USA. skoh@umaryland.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Annexin A5 / metabolism
Apoptosis / drug effects
Cadherins / genetics,  metabolism*
Cattle
Cell Survival / drug effects
Dose-Response Relationship, Drug
Endothelial Cells / drug effects*
Epithelium, Corneal / cytology*
Gene Expression Regulation / drug effects*
Glycogen / metabolism
Hydrogen Peroxide / toxicity
Necrosis / chemically induced,  prevention & control*
Oxidants / toxicity
Oxidative Stress / drug effects,  physiology
Propidium / diagnostic use
Proto-Oncogene Proteins / genetics,  metabolism*
RNA, Messenger / metabolism
Vasoactive Intestinal Peptide / pharmacology*
Grant Support
ID/Acronym/Agency:
R01 EY011607-08/EY/NEI NIH HHS; R01EY-11607/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Cadherins; 0/Oxidants; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 36015-30-2/Propidium; 37221-79-7/Vasoactive Intestinal Peptide; 56-65-5/Adenosine Triphosphate; 7722-84-1/Hydrogen Peroxide; 9005-79-2/Glycogen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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