O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation.
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.
Yang
Won Ho
WH
Department of Biology, Yonsei University, Seoul 120-749, Republic of Korea.
Park
Sang Yoon
SY
Ji
Suena
S
Kang
Jeong Gu
JG
Kim
Ji-Eun
JE
Song
Hyundong
H
Mook-Jung
Inhee
I
Choe
Kwang-Min
KM
Cho
Jin Won
JW
D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D002460:Cell Line; D003920:Diabetes Mellitus / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D051381:Rats; D000094765:Glutathione Peroxidase GPX1
D005979:Glutathione Peroxidase; D000117:Acetylglucosamine; D000094765:Glutathione Peroxidase GPX1