Phytoglycoprotein (24 kDa) inhibits expression of PCNA via PKCalpha and MAPKs in oxygen radical-stimulated Chang liver cells.
The purpose of this study was to investigate the inhibitory effect of 24-kDa glycoprotein isolated from Zanthoxylum piperitum DC fruit (ZPDC glycoprotein) on glucose/glucose oxidase (G/GO)- or hypoxanthine/xanthine oxidase (HX/XO)-induced cell proliferation in Chang liver cells. We found that ZPDC glycoprotein has significant scavenging effect on the production of intracellular H2O2 without cytotoxicity in G/GO- or HX/XO-treated in Chang liver cells. In the G/GO or HX/XO-stimulated protein kinases activity, ZPDC glycoprotein inhibited translocation of protein kinase C alpha (PKCalpha) to membrane and phosphorylation of extracellular signal-regulated kinase, p38 MAP kinase and c-Jun N-terminal kinase, respectively. In the G/GO or HX/XO-stimulated transcriptional activity, ZPDC glycoprotein also blocked the DNA binding activities of nuclear factor-kappa B and activator protein-1 and attenuated the activities of p50, p65, c-Jun and c-Fos, respectively. Finally, in the G/GO or HX/XO-stimulated cell proliferation, the activity of proliferating cell nuclear antigen was significantly blocked by treatment with ZPDC glycoprotein as well as protein kinase C inhibitor and mitogen-activated protein kinase inhibitors. On the basis of these results, we speculate that this glycoprotein is one of the natural antioxidants and of the modulators on abnormal activation of cell proliferation-related molecules in Chang liver cells.
Lee
Sei-Jung
SJ
Molecular Biochemistry Laboratory, Biotechnology Research Institute and Center for the Control of Animal Hazards Using Biotechnology (BK 21), Chonnam National University, Kwang-ju 500-757, South Korea.
Lim
Kye-Taek
KT
D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005656:Fungal Proteins / Q000494:pharmacology*; D006023:Glycoproteins / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000235:genetics*; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D032106:Zanthoxylum
D005656:Fungal Proteins; D006023:Glycoproteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D006861:Hydrogen Peroxide; D051571:Protein Kinase C-alpha; D048049:Extracellular Signal-Regulated MAP Kinases