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.

Abstract

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
• Journal: Journal of neurochemistry (J Neurochem) Vol. 109 Issue 3 Pg. 792-806 (May 2009) ISSN: 1471-4159 [Electronic] England
• PMID: 19250342 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Cadherins
• Oxidants
• Proto-Oncogene Proteins
• RNA, Messenger
• Propidium
• Vasoactive Intestinal Peptide
• Adenosine Triphosphate
• Glycogen
• Hydrogen Peroxide

Topics

• 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)
• In Vitro Techniques
• Necrosis (chemically induced, prevention & control)
• Oxidants (toxicity)
• Oxidative Stress (drug effects, physiology)
• Propidium
• Proto-Oncogene Proteins (genetics, metabolism)
• RNA, Messenger (metabolism)
• Vasoactive Intestinal Peptide (pharmacology)