Document Detail


NBHA reduces acrolein-induced changes in ARPE-19 cells: possible involvement of TGFβ.
MedLine Citation:
PMID:  21309688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Acrolein, a toxic, reactive aldehyde formed metabolically and environmentally, has been implicated in the damage to and dysfunction of the retinal pigment epithelium (RPE) that accompanies age-related macular degeneration (AMD). Our purpose was to investigate the potential of acrolein to influence the release of transforming growth factor beta-2 (TGFβ2) and vascular endothelial growth factor (VEGF), to assess the ability of N-benzylhydroxylamine (NBHA) to prevent the effect of acrolein on cytokine release and reduction of viable cells, and to explore the pathway by which acrolein might be causing the increase of VEGF.
MATERIALS AND METHODS: Confluent ARPE-19 cells were treated with acrolein and/or NBHA. They were also pretreated with SIS3, a specific inhibitor of SMAD 3, and ZM39923, a JAK3 inhibitor, before being treated with acrolein. Viable cells were counted; ELISA was used to measure the TGFβ2 and/or VEGF in the conditioned media.
RESULTS: Acrolein was shown to reduce the number of viable ARPE-19 cells and to upregulate the release of the proangiogenic cytokines TGFβ2 and VEGF. Co-treatment with 200 μM NBHA significantly reduced the effects of acrolein on viable cell number and TGFβ2 release. Pretreatment of the cells with SIS3 partially blocked the action of acrolein on decreased viable cell number and VEGF upregulation, suggesting that part of the effects of acrolein are mediated by the increased levels of TGFβ and its signaling.
CONCLUSIONS: Our results suggest that the action of acrolein on the reduction of viability and VEGF increase by ARPE-19 cells is partially mediated by TGFβ2. By reducing the effects of acrolein, NBHA and SIS3 could be potential pharmacological agents in the prevention and progression of acrolein-induced damage to the RPE that relates to AMD.
Authors:
Eileen Vidro-Kotchan; Bharat Bhushan Yendluri; Terrie Le-Thai; Andrew Tsin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-10
Journal Detail:
Title:  Current eye research     Volume:  36     ISSN:  1460-2202     ISO Abbreviation:  Curr. Eye Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-16     Completed Date:  2011-06-29     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  370-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acrolein / antagonists & inhibitors*,  toxicity
Cell Line
Cell Survival / drug effects
Enzyme-Linked Immunosorbent Assay
Humans
Hydroxylamines / pharmacology*
Isoquinolines / pharmacology
Pyridines / pharmacology
Pyrroles / pharmacology
Retinal Pigment Epithelium / drug effects*,  metabolism
Transforming Growth Factor beta2 / metabolism*
Vascular Endothelial Growth Factor A / metabolism
Grant Support
ID/Acronym/Agency:
GM08194/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/6,7-dimethyl-2-(2E)-3-(1-methyl-2-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl-prop-2-enoyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride; 0/Hydroxylamines; 0/Isoquinolines; 0/Pyridines; 0/Pyrroles; 0/Transforming Growth Factor beta2; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 2086-26-2/4-nitrobenzyloxyamine; 7864XYD3JJ/Acrolein

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