Hyperglycemia induces activation of glutathione peroxidase 1 (GPX1), an anti-oxidant enzyme essential for cell survival during oxidative stress. However, the mechanism of GPX1 activation is unclear. Here, we report that hyperglycemia-induced protein glycosylation by O-linked N-acetylglucosamine (O-GlcNAc) is crucial for activation of GPX1 and for its binding to c-Abl and Arg kinases. GPX1 itself is modified with O-GlcNAc on its C-terminus. We also demonstrate that pharmacological injection of the O-GlcNAcase inhibitor NTZ induces GPX1 activation in the mouse liver. Our findings suggest a crucial role for GPX1 and its O-GlcNAc modification in hyperglycemia and diabetes mellitus.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2010 Jan 1|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology