Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic beta-Cell Injury
Diabetes & Metabolism Journal
;
: 469-479, 2011.
Artigo
em Inglês
| WPRIM
| ID: wpr-22257
ABSTRACT
BACKGROUND:
Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic beta-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic beta-cells from high glucose-induced apoptosis.METHODS:
Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.RESULTS:
CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.CONCLUSION:
Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Protoporfirinas
/
RNA Mensageiro
/
Regulação para Cima
/
Sobrevivência Celular
/
Espécies Reativas de Oxigênio
/
Apoptose
/
Diabetes Mellitus
/
Heme Oxigenase-1
/
Caspase 3
/
Citometria de Fluxo
Idioma:
Inglês
Revista:
Diabetes & Metabolism Journal
Ano de publicação:
2011
Tipo de documento:
Artigo
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