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- Title
Overexpression of O-GlcNAcase Improves the Mitochondrial Function Impaired by Hyperglycemia in Cardiomyocytes.
- Authors
Hu, Yong; Suarez, Jorge; Dillmann, Wolfgang
- Abstract
Excessive protein O-GlcNAcylation has been shown in the diabetic heart to contribute to cardiac dysfunction, and reducing this excess cellular O-GlcNAcylation, has beneficial effects on calcium handling and diabetic cardiac function. Recently, we found that some mitochondrial proteins were also O-GlcNAc modified. Hyperglycemia elevated the mitochondrial O-GlcNAcylation level and overexpressing O-GlcNAcase, the enzyme removing the O-GlcNAc modification from the proteins, decreased O-GlcNAc modification level of mitochondria. To explore the role of O-GlcNAc on dysfunction of the mitochondria in diabetic heart, we treated the neonatal cardiomyocytes with different glucose (5mM and 30mM glucose). The results showed that compared with normal glucose treatment (5mM), hyperglycemia (30mM) impaired the activities of complex III and complex IV of the respiratory chain (RC) in cardiomyocytes. Overexpressing O-GlcNAcase recovered the activity of the mitochondrial RC complex Ill and 1V caused by hyperglycemia condition (30mM glucose). The cellular ATP content was determined by bioluminescence with the luciferin/luciferase reactions. In high glucose condition, myocytes showed lower cellular ATP level than it in normal glucose condition; and O-GlcNAcase overexpressed myocytes showed higher ATP level than it in same high glucose condition. We also found that high glucose induced decrease in mitochondrial Ca levels and overexpressing O-GlcNAcase recovered mitochondrial Ca level. From these data, we concluded that hyperglycermia increases cardiomyotes mitochondrial O-GlcNAcylation, which contributes to the impaired mitochondrial function by high glucose.
- Publication
Diabetes, 2007, Vol 56, pA192
- ISSN
0012-1797
- Publication type
Academic Journal