Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation.
In: Diabetes, Jg. 51 (2002), Heft 1, S. 159-167
Online
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Zugriff:
Apoptosis has been observed in vascular cells, nerve, and myocardium of diabetic humans and experimental animals, although whether it contributes to or is a marker of complications in these tissues is unclear. Previous studies have shown that incubation of human umbilical vein endothelial cells (HUVECs) with 30 vs. 5 mmol/l glucose for 72 h causes a significant increase in apoptosis, possibly related to an increase in oxidative stress. We report here that this increase in apoptosis (assessed morphologically by TdT-mediated dUTP nick- end labeling staining) is preceded (24 h of incubation) by inhibition of fatty acid oxidation, by increases in diacylglycerol synthesis, the concentration of malonyl CoA, and caspase-3 activity, and by decreases in mitochondrial membrane potential and cellular ATP content. In addition, the phosphorylation of Akt in the presence of 150 microU/ml insulin was impaired. No increases in ceramide content or its de novo synthesis were observed. AMP-activated protein kinase (AMPK) activity was not diminished; however, incubation with the AMPK activator 5-aminoimidazole-4-carboxamide-riboside increased AMPK activity twofold and completely prevented all of these changes. Likewise, expression of a constitutively active AMPK in HUVEC prevented the increase in caspase-3 activity. The results indicate that alterations in fatty-acid metabolism, impaired Akt activation by insulin, and increased caspase-3 activity precede visible evidence of apoptosis in HUVEC incubated in a hyperglycemic medium. They also suggest that AMPK could play an important role in protecting the endothelial cell against the adverse effects of sustained hyperglycemia. [ABSTRACT FROM AUTHOR]
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Titel: |
Hyperglycemia-induced apoptosis in human umbilical vein endothelial cells: inhibition by the AMP-activated protein kinase activation.
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Autor/in / Beteiligte Person: | Ido, Yasuo ; Carling, David ; Ruderman, Neil |
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Zeitschrift: | Diabetes, Jg. 51 (2002), Heft 1, S. 159-167 |
Veröffentlichung: | 2002 |
Medientyp: | academicJournal |
ISSN: | 0012-1797 (print) |
DOI: | 10.2337/diabetes.51.1.159 |
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