title: Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells.
abstract: The mechanisms related to hyperglycemia-induced pancreatic beta-cell apoptosis are poorly defined. Rat insulin-producing cells (RINm5F) cultured in high glucose concentrations (30 mM) showed increased apoptosis and protein p53 translocation to mitochondria. In addition, hyperglycemia induced both the disruption of mitochondrial membrane potential (Delta psi (m)), and an increase in reactive oxygen species (ROS), as shown by fluorescence changes of JC-1 and dichlorodihydrofluorescein-diacetate (DCDHF-DA), respectively. The increased intracellular ROS by high glucose exposure was blunted by mitochondrial-function and NADPH-oxidase inhibitors. We postulate that the concomitant mobilization of p53 protein to the mitochondria and the subsequent changes on the Delta psi (m), lead to an important pancreatic beta-cell apoptosis mechanism induced by oxidative stress caused by hyperglycemia.
authors.affiliation: Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades CMNS XXI, Instituto Mexicano del Seguro Social, México. leimich@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: Ortega-Camarillo
authors.forename: A M
authors.initials: AM
authors.lastname: Guzmán-Grenfell
authors.forename: R
authors.initials: R
authors.lastname: García-Macedo
authors.forename: A M
authors.initials: AM
authors.lastname: Rosales-Torres
authors.forename: A
authors.initials: A
authors.lastname: Avalos-Rodríguez
authors.forename: G
authors.initials: G
authors.lastname: Durán-Reyes
authors.forename: R
authors.initials: R
authors.lastname: Medina-Navarro
authors.forename: M
authors.initials: M
authors.lastname: Cruz
authors.forename: M
authors.initials: M
authors.lastname: Díaz-Flores
authors.forename: J
authors.initials: J
authors.lastname: Kumate
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000502:physiology; D018613:Microscopy, Confocal; D051336:Mitochondrial Membranes / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53