title: O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation.
abstract: 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.
authors: Department of Biology, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Won Ho
authors: WH
authors: Yang
authors: Sang Yoon
authors: SY
authors: Park
authors: Suena
authors: S
authors: Ji
authors: Jeong Gu
authors: JG
authors: Kang
authors: Ji-Eun
authors: JE
authors: Kim
authors: Hyundong
authors: H
authors: Song
authors: Inhee
authors: I
authors: Mook-Jung
authors: Kwang-Min
authors: KM
authors: Choe
authors: Jin Won
authors: JW
authors: Cho
mesh_terms: 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
chemical_list: D005979:Glutathione Peroxidase; D000117:Acetylglucosamine; D000094765:Glutathione Peroxidase GPX1