title: Hydrogen peroxide increases [3H]-2-deoxyglucose uptake via MAPKs, cPLA2, and NF-kappaB signaling pathways in mouse embryonic stem cells.
abstract: Hydrogen peroxide (H(2)O(2)) has been shown to act as a signaling molecule that is involved in many cellular functions. This study investigated the effect of H(2)O(2) on the [3H]-2-deoxyglucose (2-DG) uptake and its related signaling pathways in mouse embryonic stem (ES) cells. H(2)O(2) significantly increased the level of 2-DG uptake in a time- (> 4 hr) and concentration- (>10-4 M) dependent manner due to an increase in V(max) but not K(m). Indeed, H(2)O(2) increased the mRNA and protein level of glucose transporter 1 (GLUT 1). PD 98059 (a p44/42 MAPKs inhibitor, 10-5 M), SB 203580 (a p38 MAPK inhibitor, 10-6 M), and SP 600125 (a SAPK/JNK inhibitor, 10-6 M) blocked the H(2)O(2)-induced increase in 2-DG uptake. H(2)O(2) also increased phosphorylation of p44/42 mitogen activated protein kinases (MAPKs), p38 MAPK, and stress-activated protein kinase/Jun-N-terminal kinase (SAPK/JNK). In addition, H(2)O(2) stimulated the translocation of cytosolic phospholipase A(2) (cPLA(2)) from the cytosolic fraction to the membrane fraction, the release of arachidonic acid, and the activation of NF-kappaB. AACOCF(3) or mepacrine (cPLA(2) inhibitors, 10-6 M), SN 50 (NF-kappaB nucleus translocation inhibitor, 500 ng/ml) or Bay11-7082 (a IkappaB-alpha phosphorylation inhibitor, 2x10-5 M) blocked the H(2)O(2)-induced increase in 2-DG uptake. H(2)O(2) increased the protein level of glucose transporter 1 (GLUT 1), which was blocked by PD 98059, SB 203580, SP 600125, mepacrine, or Bay11-7082. In conclusion, H(2)O(2) increases the 2-DG uptake via MAPKs, cPLA(2), and NF-kappaB signaling pathways in mouse ES cells.
authors.affiliation: Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University.
authors.forename: Sun Im
authors.initials: SI
authors.lastname: Na
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Heo
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D014316:Tritium
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000975:Antioxidants; D051272:Glucose Transporter Type 1; D016328:NF-kappa B; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D013450:Sulfones; D014316:Tritium; D016718:Arachidonic Acid; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D054513:Group IV Phospholipases A2; D011796:Quinacrine