Abstract | PURPOSE: 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.
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Authors | Eileen Vidro-Kotchan, Bharat Bhushan Yendluri, Terrie Le-Thai, Andrew Tsin |
Journal | Current eye research
(Curr Eye Res)
Vol. 36
Issue 4
Pg. 370-8
(Apr 2011)
ISSN: 1460-2202 [Electronic] England |
PMID | 21309688
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- 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
- Hydroxylamines
- Isoquinolines
- Pyridines
- Pyrroles
- Transforming Growth Factor beta2
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- 4-nitrobenzyloxyamine
- Acrolein
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Topics |
- 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)
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