PMID- 17975303 OWN - NLM STAT- MEDLINE DCOM- 20071219 LR - 20190212 IS - 1015-8987 (Print) IS - 1015-8987 (Linking) VI - 20 IP - 6 DP - 2007 TI - Hydrogen peroxide increases [3H]-2-deoxyglucose uptake via MAPKs, cPLA2, and NF-kappaB signaling pathways in mouse embryonic stem cells. PG - 1007-18 AB - 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. FAU - Na, Sun Im AU - Na SI AD - Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University. FAU - Lee, Min Young AU - Lee MY FAU - Heo, Jung Sun AU - Heo JS FAU - Han, Ho Jae AU - Han HJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071029 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile) RN - 0 (Antioxidants) RN - 0 (Glucose Transporter Type 1) RN - 0 (NF-kappa B) RN - 0 (Nitriles) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Sulfones) RN - 10028-17-8 (Tritium) RN - 27YG812J1I (Arachidonic Acid) RN - 9G2MP84A8W (Deoxyglucose) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.1.1.4 (Group IV Phospholipases A2) RN - H0C805XYDE (Quinacrine) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Arachidonic Acid/metabolism MH - Deoxyglucose/*metabolism MH - Dose-Response Relationship, Drug MH - Embryonic Stem Cells/*drug effects/*enzymology/metabolism MH - Enzyme Activation/drug effects MH - Gene Expression Regulation/drug effects MH - Glucose Transporter Type 1/genetics/metabolism MH - Group IV Phospholipases A2/*metabolism MH - Hydrogen Peroxide/*pharmacology MH - Kinetics MH - MAP Kinase Signaling System/*drug effects MH - Mice MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism MH - NF-kappa B/*metabolism MH - Nitriles/pharmacology MH - Protein Kinase Inhibitors/pharmacology MH - Quinacrine/pharmacology MH - Sulfones/pharmacology MH - Time Factors MH - Tritium EDAT- 2007/11/03 09:00 MHDA- 2007/12/20 09:00 CRDT- 2007/11/03 09:00 PHST- 2007/11/03 09:00 [pubmed] PHST- 2007/12/20 09:00 [medline] PHST- 2007/11/03 09:00 [entrez] AID - 110541 [pii] AID - 10.1159/000110541 [doi] PST - ppublish SO - Cell Physiol Biochem. 2007;20(6):1007-18. doi: 10.1159/000110541. Epub 2007 Oct 29.