Antioxidant N-acetyl-cysteine protects retinal pigmented epithelial cells from long-term hypoxia changes in gene expression.
OBJECTIVE
To further know the signaling pathways involved in hypoxia-induced apoptosis in retinal pigmented epithelial (RPE) cells and to improve the understanding of the antioxidant N-acetyl-cysteine (NAC) treatment effect.


METHODS
We analyzed the expression levels of several apoptosis-related genes by semiquantitative reverse transcriptase-polymerase chain reaction in RPE after 72 h of maintained hypoxia, with or without 10 mM NAC treatment.


RESULTS
Under hypoxic conditions, we detected a higher expression level of p53 and CASP8. Cell treatment with NAC 10 mM prevented this increase. Other apoptosis-related genes such as bax, CASP3, CASP4, CASP7, and fas did not show an increase in expression levels in hypoxia.


CONCLUSIONS
NAC prevents the increased expression levels of p53 and CASP8 induced by long-term maintained hypoxia. The supply of antioxidants could be a useful preventive approach in protecting RPE from the effects of chronic oxygen stress, which is of great interest in oxygen stress-related diseases such as age-related macular degeneration and other senescence-associated pathologies.
Gerona
Guillermo
G
Departamento de Optica, Farmacología y Anatomía, Universidad de Alicante , San Vicente del Raspeig, Spain.
López
Damián
D
Palmero
Mercedes
M
Maneu
Victoria
V
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D016158:Genes, p53; D018384:Oxidative Stress / Q000187:drug effects; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3; D053181:Caspase 8; D000111:Acetylcysteine