Document Detail


Differential effects of nicotine on retinal and vascular cells in vitro.
MedLine Citation:
PMID:  19428945     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of the current study is to understand the effects of nicotine in human retinal pigment epithelial (ARPE-19), human microvascular endothelial cells (HMVEC) and rat neurosensory retinal (R28) cells. ARPE-19, HMVEC and R28 cell cultures were treated with 10(-2) and 10(-4)M nicotine for 24h. R28 cells were also pre-treated for 4h with ALLN and ALLM (calpain inhibitors) or epicatechin, an antioxidant flavonoid compound. Trypan blue dye exclusion assay, caspase-3/7, LDH activity and DNA laddering assays were performed. With 10(-2)M nicotine treatment, R28 cell cultures showed decreased cell viability that was partially reversed by pre-treatment with the antioxidant epicatechin but not with calpain inhibitors. The DNA ladder assay showed a 200bp banding pattern consistent with apoptosis, however, caspase-3/7 activity was not increased. After treatment with 10(-2)M nicotine, HMVEC cultures showed decreased cell viability and increased LDH activity but no DNA banding patterns or caspase-3/7 activity. ARPE-19 cells showed no change in cell viability or caspase-3/7 activity at any of the nicotine concentrations. We conclude of dissimilar responses to nicotine treatment in three different cell lines. Nicotine was toxic to HMVEC and R28 cell cultures but the ARPE-19 cells were unaffected. In R28 cells, the nicotine effects were through an oxidant pathway that is non-caspase, non-calpain mediated while the HMVEC toxicity was via necrosis. Understanding the mechanisms of cell death may have potential therapeutic implications in the treatment of cigarette smoking related retinal diseases such as age-related macular degeneration (AMD).
Authors:
A Jayaprakash Patil; Ana L Gramajo; Ashish Sharma; Gail M Seigel; Baruch D Kuppermann; M Cristina Kenney
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-20
Journal Detail:
Title:  Toxicology     Volume:  259     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  69-76     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Gavin S. Herbert Eye Institute, University of California Irvine, Medical Center, 101 The City Drive, Orange, CA 92868, United States.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Caspase 3 / drug effects,  metabolism
Caspase 7 / drug effects,  metabolism
Catechin / pharmacology
Cell Line
Cell Survival / drug effects
Cells, Cultured
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Endothelial Cells / drug effects*,  metabolism
Humans
L-Lactate Dehydrogenase / drug effects,  metabolism
Necrosis / chemically induced
Nicotine / administration & dosage,  toxicity*
Nicotinic Agonists / administration & dosage,  toxicity*
Rats
Retina / cytology,  drug effects*,  metabolism
Retinal Pigment Epithelium / drug effects*,  metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Nicotinic Agonists; 154-23-4/Catechin; 54-11-5/Nicotine; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7

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


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