title: Somatostatin protects photoreceptor cells against high glucose-induced apoptosis.
abstract: Many cellular and molecular studies in experimental animals and early retinal function tests in patients with diabetic retinopathy (DR) have shown that retinal neurodegeneration is an early event in the pathogenesis of the disease. Somatostatin (SST) is one of the most important neuroprotective factors synthesized by the retina: SST levels are decreased in parallel to retinal neurodegeneration in early stages of DR. In this study, we characterized the induction of apoptosis (programmed cell death) in a 661W photoreceptor-like cell line cultured under high glucose (HG) conditions and the effect of SST.
  
  
  
  A 661W photoreceptor-like cell line and retinal explants from 10-week-old male C57BL/6 mice were cultured under HG conditions and treated with SST.
  
  
  
  Hyperglycemia significantly reduced the cellular viability by increasing the percentage of apoptotic cells, and this effect was ameliorated by SST (p˂0.05). Activation of caspase-8 by hyperglycemia was found in the 661W cells and retinal explants and decreased in the presence of SST (p˂0.05). Moreover, we detected activation of calpain-2 associated with hyperglycemia-induced cell death, as well as increased protein tyrosine phosphatase 1B (PTP1B) protein levels; both had a pattern of cleavage that was absent in the presence of SST (p˂0.05). Treatment of the 661W cells and retinal explants with SST for 24 h increased the phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR; tyrosine 1165/1166) and protein kinase B (Akt; serine 473), suggesting this survival signaling is activated in the neuroretina by SST (p˂0.05).
  
  
  
  This study has provided new mechanistic insights first into the involvement of calpain-2 and PTP1B in the loss of cell survival and increased caspase-8-dependent apoptosis induced by hyperglycemia in photoreceptor cells and second, on the protective effect of SST against apoptosis by the enhancement of IGF-IR-mediated Akt phosphorylation.
authors.affiliation: Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), 28029 Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Madrid, Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Arroba
authors.forename: Aurora
authors.initials: A
authors.lastname: Mazzeo
authors.affiliation: Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), 28029 Madrid, Spain.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cazzoni
authors.forename: Elena
authors.initials: E
authors.lastname: Beltramo
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernández
authors.forename: Massimo
authors.initials: M
authors.lastname: Porta
authors.affiliation: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Simó
authors.affiliation: Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), 28029 Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, Madrid, Spain.
authors.forename: Ángela M
authors.initials: ÁM
authors.lastname: Valverde
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D006943:Hyperglycemia / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*
chemical_list: D013004:Somatostatin; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D002154:Calpain; D053181:Caspase 8; D005947:Glucose