PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells.
Jia HeChongde LongZixin HuangXin ZhouXielan KuangLanying LiuHuijun LiuYan TangYuting FanJie NingXinqi MaQingjiong ZhangHuangxuan ShenPublished in: BioMed research international (2017)
Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α (one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.
Keyphrases
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- cell cycle arrest
- signaling pathway
- dna damage
- pi k akt
- diabetic rats
- cell proliferation
- cell death
- poor prognosis
- age related macular degeneration
- cystic fibrosis
- staphylococcus aureus
- multiple sclerosis
- heat shock
- transcription factor
- pseudomonas aeruginosa
- heat stress
- biofilm formation