title: Calcium-independent phospholipase A₂, group VIA, is critical for RPE cell survival.
abstract: OBJECTIVE
  To investigate the significance of calcium-independent phospholipase A₂, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures.
  
  
  METHODS
  The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were treated with SI to induce cell death. Cells were transfected with an iPLA₂-VIA promoter-luciferase construct to evaluate the regulation of iPLA-VIA after exposure to SI. PCR analysis, western blot analysis, and activity assays were performed to evaluate the mRNA level, protein level, and activity levels of iPLA₂-VIA after SI exposure. Inhibitors of iPLA₂-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA₂-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against SI in iPLA₂-VIA knockout mice compared to wild-type mice.
  
  
  RESULTS
  The study revealed upregulation of iPLA₂-VIA expression (promoter activity, iPLA₂-VIA mRNA, iPLA₂-VIA protein, and iPLA₂-VIA protein activity) in ARPE-19 cells exposed to SI. SI-induced cell death was shown to be inhibited by iPLA₂-VIA-specific inhibitors in ARPE-19 cell cultures. RPE cultures from iPLA₂-VIA knockout mice were less vulnerable to SI-induced cell death compared to RPE cultures from wild-type mice.
  
  
  CONCLUSIONS
  SI -induced RPE cell death involves iPLA₂-VIA upregulation and activation, and amelioration of SI-induced RPE cell death can be facilitated by inhibitors of iPLA₂-VIA. Thus, we suggest iPLA₂-VIA as a possible pharmaceutical target to treat RPE-related retinal diseases.
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark ; Roskilde University Hospital, Department of Ophthalmology, Copenhagen, Denmark ; Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Miriam
authors.initials: M
authors.lastname: Kolko
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rupali
authors.initials: R
authors.lastname: Vohra
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Barbro
authors.initials: B
authors.lastname: Westlund van der Burght
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark ; Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Poulsen
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mogens Holst
authors.initials: MH
authors.lastname: Nissen
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007452:Iodates / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D007452:Iodates; D012333:RNA, Messenger; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human; D054510:Phospholipases A2, Cytosolic; C516476:Pla2g6 protein, mouse; C032285:sodium iodate