title: Paraoxonase enzyme protects retinal pigment epithelium from chlorpyrifos insult.
abstract: Retinal pigment epithelium (RPE) provides nourishment and protection to the eye. RPE dysfunction due to oxidative stress and inflammation is one of the major reason for many of the retinal disorders. Organophosphorus pesticides are widely used in the agricultural, industrial and household activities in India. However, their effects on the eye in the context of RPE has not been studied. In this study the defense of the ARPE19 cells exposed to Chlorpyrifos (1 nM to 100 µM) in terms of the enzyme paraoxonase (PON) was studied at 24 hr and 9 days of treatment. Chlorpyrifos was found to induce oxidative stress in the ARPE19 cells as seen by significant increase in ROS and decrease in glutathione (GSH) levels without causing cell death. Tissue resident Paraoxonase 2 (PON2) mRNA expression was elevated with chlorpyrifos exposure. The three enzymatic activities of PON namely, paraoxonase (PONase), arylesterase (PON AREase) and thiolactonase (PON HCTLase) were also found to be significantly altered to detoxify and as an antioxidant defense. Among the transcription factors regulating PON2 expression, SP1 was significantly increased with chlorpyrifos exposure. PON2 expression was found to be crucial as ARPE19 cells showed a significant loss in their ability to withstand oxidative stress when the cells were subjected to chlorpyrifos after silencing PON2 expression. Treatment with N-acetyl cysteine positively regulated the PON 2 expression, thus promoting the antioxidant defense put up by the cells in response to chlorpyrifos.
authors: R.S Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO Block, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Jagan Mohan
authors: JM
authors: Jasna
authors: R.S Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO Block, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Kannadasan
authors: K
authors: Anandbabu
authors: R.S Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO Block, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Subramaniam Rajesh
authors: SR
authors: Bharathi
authors: R.S Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO Block, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors: Narayanasamy
authors: N
authors: Angayarkanni
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004390:Chlorpyrifos / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D062025:Organophosphate Poisoning / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000201:enzymology*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D007306:Insecticides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016329:Sp1 Transcription Factor; D043303:Aryldialkylphosphatase; C468411:PON2 protein, human; D005978:Glutathione; D004390:Chlorpyrifos