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NBHA Reduces Acrolein-Induced Changes in ARPE-19 Cells: Possible Involvement of TGF?
MedLine Citation:
PMID:  21309688     Owner:  NLM     Status:  Publisher    
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 (TGF?2) 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 TGF?2 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 TGF?2 and VEGF. Co-treatment with 200 ?M NBHA significantly reduced the effects of acrolein on viable cell number and TGF?2 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 TGF? 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 TGF?2. 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.
Eileen Vidro-Kotchan; Bharat Bhushan Yendluri; Terrie Le-Thai; Andrew Tsin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-10
Journal Detail:
Title:  Current eye research     Volume:  -     ISSN:  1460-2202     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
The University of Texas at San Antonio, San Antonio, Texas, USA.
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