Hydrogen peroxide increases [3H]-2-deoxyglucose uptake via MAPKs, cPLA2, and NF-kappaB signaling pathways in mouse embryonic stem cells.
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.
Na
Sun Im
SI
Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University.
Lee
Min Young
MY
Heo
Jung Sun
JS
Han
Ho Jae
HJ
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
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