Abstract | PURPOSE: To understand better the cell and molecular basis for the epidemiologic association between cigarette smoke, oxidant injury, and age-associated macular degeneration, the authors examined the effects of acrolein, a major toxicant in cigarette smoke, on oxidative mitochondrial damage in retinal pigment epithelial (RPE) cells and the reduction of this damage by lipoic acid. METHODS: Cultured human ARPE19 cells and primary cultures of human fetal (hf)RPE were treated with acrolein. The toxicity of acrolein and the protective effects of R- alpha-lipoic acid were examined with a variety of previously described techniques. RESULTS: Acute acrolein exposure exceeding 50 microM (24 hours) in ARPR19 cells caused toxicity, including decreases in cell viability, mitochondrial potential, GSH, antioxidant capacity, Nrf2 expression, enzyme activity (mitochondrial complexes I, II, III; superoxide dismutase; and glutathione peroxidase). Acute exposure also increased oxidant levels, protein carbonyls, and calcium. Continuous acrolein exposure over 8 or 32 days caused similar toxicity but from 10- to 100-fold lower doses (0.1-5 microM). Pretreatment with R- alpha-lipoic acid effectively protected ARPE-19 cells from acrolein toxicity. Primary hfRPE cells were comparable to the ARPE-19 cells in sensitivity to acrolein toxicity and lipoic acid protection. CONCLUSIONS: These results show that acrolein is a mitochondrial toxicant in RPE cells and that acrolein-induced oxidative mitochondrial dysfunction is reduced by lipoic acid. The similar sensitivity of the ARPE-19 and hfRPE cells suggests that both models are useful for studying RPE toxicity and protection. These experiments indicate that mitochondria-targeted antioxidants such as lipoic acid may be an effective strategy for reducing or preventing chronic oxidant-induced RPE degeneration in vivo from a variety of sources, including cigarette smoke.
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Authors | Lihong Jia, Zhongbo Liu, Lijuan Sun, Sheldon S Miller, Bruce N Ames, Carl W Cotman, Jiankang Liu |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 48
Issue 1
Pg. 339-48
(Jan 2007)
ISSN: 0146-0404 [Print] United States |
PMID | 17197552
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Electron Transport Chain Complex Proteins
- NF-E2-Related Factor 2
- NFE2L2 protein, human
- Tobacco Smoke Pollution
- Thioctic Acid
- Acrolein
- Glutathione Peroxidase
- Superoxide Dismutase
- Glutathione
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Topics |
- Acrolein
(toxicity)
- Antioxidants
(pharmacology)
- Cell Line
- Cell Survival
- Cytoprotection
(drug effects)
- Electron Transport Chain Complex Proteins
(metabolism)
- Glutathione
(metabolism)
- Glutathione Peroxidase
(metabolism)
- Humans
- Membrane Potential, Mitochondrial
- Mitochondrial Diseases
(chemically induced, metabolism, prevention & control)
- NF-E2-Related Factor 2
(metabolism)
- Oxidative Stress
(drug effects)
- Pigment Epithelium of Eye
(drug effects, metabolism)
- Superoxide Dismutase
(metabolism)
- Thioctic Acid
(pharmacology)
- Tobacco Smoke Pollution
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