PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling.
OBJECTIVE
Oxidative stress that damages cells of the retinal pigment epithelium (RPE) can cause the development of hereditary retinal disease (HRD). PRDX6, which is a member of the PRDX family, is essential for removing metabolic free radicals from the body. However, the effect of PRDX6 on oxidative stress in HRD remains unknown. In this study, we sought to investigate the role of PRDX6 in oxidative stress-induced HRD in ARPE-19 cells and the molecular mechanism involved.


METHODS
ARPE-19 cells were used in the current study. Intracellular ROS levels were determined by flow cytometry. Lipid peroxidation was measured using a commercial MDA assay kit. Cellular variability was determined by MTT assay. Apoptosis was determined using an Annexin V-FITC Apoptosis Detection Kit. mRNA and protein expression levels were detected by real-time PCR and western blot analysis, respectively.


RESULTS
We found that H2O2 and blue light could induce significant oxidative stress damage and cell death in ARPE-19 cells. Furthermore, we found that PRDX6 levels significantly decreased after H2O2 treatment. PRDX6 overexpression protected ARPE-19 cells from H2O2- and blue light-induced oxidative damage, while PRDX6 knockdown enhanced oxidative damage in these cells. Mechanistically, we found that PRDX6 prevented oxidative damage and promoted ARPE-19 cell survival through the PI3K/AKT signaling pathway.


CONCLUSIONS
Collectively, these results suggest that PRDX6 protects ARPE-19 cells from H2O2-induced oxidative stress and apoptosis and that this protection is mediated at least partially through the PI3K/AKT pathway.
Department of the Ophthalmology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Xu
X
Zha
Guojiu
G
Wu
Xueying
X
Zhao
Liqiong
L
Zhou
Hong
H
Zhang
Jinghua
J
Li
Linkun
L
Ma
Yuanping
Y
Zhang
D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008027:Light; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D012333:RNA, Messenger; D006861:Hydrogen Peroxide; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt