title: Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine.
abstract: Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.
authors.affiliation: Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany; Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany; Department of Cardiology, Pulmonology, Intensive Care and Vascular Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Ntasis
authors.affiliation: Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kabtni
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: van den Born
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.affiliation: Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
authors.affiliation: Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Sibylle J
authors.initials: SJ
authors.lastname: Hauske
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002331:Carnitine / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D019610:Cytoprotection; D004150:Dipeptidases / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005290:Ferric Compounds / Q000633:toxicity*; D005947:Glucose / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011990:Receptors, Transferrin / Q000378:metabolism; D014162:Transfection; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D015703:Antigens, CD; D002331:Carnitine; D027682:Cation Transport Proteins; D002712:Chlorides; D004150:Dipeptidases; D005290:Ferric Compounds; D005947:Glucose; D007502:Iron Chelating Agents; D011990:Receptors, Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C068126:CD71 antigen; C522928:CNDP1 protein, human; C024555:ferric chloride