title: Selenium effectively inhibits 1,2-dihydroxynaphthalene-induced apoptosis in human lens epithelial cells through activation of PI3-K/Akt pathway.
abstract: OBJECTIVE
  To investigate whether activation of the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (Akt) pathway was necessary for selenium in protecting human lens epithelial cells (hLECs) from 1,2-dihydroxynaphthalene (1,2-DHN)-induced apoptosis. In addition, we studied the link between heat shock protein 70 (HSP70) expression and Akt phosphorylation in selenium-induced cell protection.
  
  
  METHODS
  Cell viabilities were assessed by Cell Counting Kit-8 (CCK-8) kit and trypan blue exclusion. The effect of sodium selenite on Akt phosphorylation was studied. After the pretreatment with 30 μM of LY294002, a PI3-K/Akt pathway inhibitor, apoptosis was assessed by flow cytometry, protein levels of phospho-Akt and Akt were quantified by western blot, and cell localization of phospho-Akt was determined by immunofluorescence staining. Time-course effect of sodium selenite on HSP70 expression was studied by reverse transcription polymerase chain reaction (RT-PCR) and western blot. Moreover, effect of LY294002 on HSP70 expression was also examined.
  
  
  RESULTS
  Our data showed that sodium selenite increased cell viabilities and prevented 1,2-DHN-induced apoptosis through phosphorylation and nuclear translocation of Akt. Furthermore, pretreatment of LY294002 inhibited the phosphorylation of Akt. However, it failed to block the selenium-induced upregulation of HSP70.
  
  
  CONCLUSIONS
  The activation of PI3-K/Akt pathway was necessary for selenium in protecting hLECs from 1,2-DHN-induced apoptosis. However, this pathway was not involved in the selenium-induced upregulation of HSP70.
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, P.R. China.
authors.forename: Xiangjia
authors.initials: X
authors.lastname: Zhu
authors.forename: Kun
authors.initials: K
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009284:Naphthols / Q000009:adverse effects / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D002867:Chromones; D018840:HSP70 Heat-Shock Proteins; D009025:Morpholines; D009284:Naphthols; D047428:Protein Kinase Inhibitors; C050642:1,2-dihydroxynaphthalene; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D012643:Selenium