期刊
TOXICOLOGY
卷 271, 期 3, 页码 107-114出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2010.03.013
关键词
Apoptosis; Reactive oxygen/nitrogen species; Mitochondrial membrane potential; ATP level; Catechol; Cigarette smoke toxicant; MIO-M1 cells; Memantine; Epicatechin
资金
- Medical Research Council [G0300259] Funding Source: Medline
- Medical Research Council [G0300259] Funding Source: researchfish
- MRC [G0900002] Funding Source: UKRI
This study evaluates the toxic effects of catechol (a component from cigarette smoke) on Muller cells (MIO-M1) in vitro, and investigates the inhibitors memantine and epicatechin to determine if they can reverse the catechol toxic effects. MIO-MI cells were exposed to varying concentrations of catechol with or without memantine or epicatechin. Cell viability (CV) was measured by a trypan blue dye-exclusion assay. Caspase-3/7 activity was measured by fluorochrome assay. The production of reactive oxygen/nitrogen species (ROS/RNS) was measured with 2',7'-dichlorodihydrofluorescein diacetate dye assay. Mitochondrial membrane potential (Delta Psi m) was measured using JC-1 assay. Intracellular ATP content was determined by the ATPLite kit. MIO-M1 cells showed significant decrease in cell viability, increased caspase-3/7 activity, elevated ROS/RNS levels, decreased Delta Psi m value, and decreased intracellular ATP content after exposure to catechol 150, 300, and 600 mu M compared with control. Pre-treatment with memantine 10 mu M or epicatechin 15 mu M reversed loss of cell viability in catechol 150 mu M-treated cultures (22.3%, p<0.01 and 17.8%, p<0.05), respectively. Similarly, pre-treatment with memantine 10 mu M and epicatechin 15 mu M prior to catechol resulted in decreased caspase-3/7 activities (77% and 64.2%, p<0.001), decreased ROS/RNS levels (82.3% and 79%, p<0.001). increased Delta Psi m value (76.4% and 72.2%, p<0.001), and increased ATP levels (46.6% and 40.4%, p<0.001) compared to 150 mu M catechol-treated cultures. Catechol, a component of smoking, can diminish cell viability and mitochondrial function in MIO-M1 cells in vitro. However, memantine and epicatechin can partially reverse the cytotoxic effect of catechol. Their administration may reduce or prevent Muller cells degeneration in AMD or other retinal degenerative disorders. (C) 2010 Published by Elsevier Ireland Ltd.
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