Oxidative stress mediates apoptotic changes induced by hyperglycemia in human tubular kidney cells.
J Am Soc Nephrol
; 15 Suppl 1: S85-7, 2004 Jan.
Article
en En
| MEDLINE
| ID: mdl-14684680
ABSTRACT
Reactive oxygen species (ROS) are important mediators for several biologic responses, including apoptosis. The present study evaluated the time course of changes in intracellular ROS production and apoptosis-related proteins, as well as apoptotic changes in human tubular proximal cells (HK-2 cells) exposed to hyperglycemia. Apoptosis (annexin V binding), ROS formation (fluorescence probe dichlorofluorescin diacetate and FACScan flow cytometry), and X chromosome-linked protein (XIAP; Western blot) were studied in HK-2 cells grown in a medium containing normal (NG) or high glucose (HG) concentrations (5.5 or 30 mM, respectively) for 18 to 48 h. HG promoted an increase (65% at 18 h and 73% at 24 h; P < 0.05 versus NG) in intracellular ROS generation. At 18 h, the NF-kB binding activity (evaluated by electrophoretic mobility-shift assay) was suppressed by HG. At the same time, the expression of NF-kB-induced antiapoptotic XIAP was reduced in HG-treated cells. Apoptotic changes were observed at 48 h (34 +/- 7% in HG versus 10 +/- 3% in NG; P < 0.001). Changes in ROS production at 24 h predicted changes in the apoptotic index at 48 h (r = 0.96, P < 0.0001). These results suggest that hyperglycemia induces apoptotic changes in human tubular cells via an increase in oxidative stress and that a downregulation of antiapoptotic protein XIAP is a component of this response.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Especies Reactivas de Oxígeno
/
Apoptosis
/
Estrés Oxidativo
/
Hiperglucemia
/
Túbulos Renales Proximales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Am Soc Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia