ANG II increases 2-deoxyglucose uptake in mouse embryonic stem cells.
It is now suggested that all components of the renin-angiotensin system are present in many tissues, including the embryo and may play a major role in embryo development and differentiation. However, little is known regarding whether ANG II regulates glucose transport in mouse embryonic stem (ES) cells. Thus, the effects of ANG II on [3H]-2-deoxyglucose (2-DG) uptake and its related signal pathways were examined in mouse ES cells. ANG II significantly increased cell proliferation and 2-DG uptake in concentration- and time-dependent manner (>18 h, >10(-8) M) and increased mRNA and protein level of GLUT1 by 31+/-7% and 22+/-5% compared to control, respectively. Actinomycin D and cycloheximide completely blocked the effect of ANG II on 2-DG uptake. ANG II-induced increase of 2-DG uptake was blocked by losartan, an ANG II type 1 (AT1) receptor blocker, but not by PD 123319, an ANG II type 2 (AT2) receptor blocker. In addition, ANG II-induced stimulation of 2-DG uptake was attenuated by phospholipase C (PLC) inhibitors, neomycin and U 73122 and ANG II increased inositol phosphates (IPs) formation by 37+/-8% of control. Protein kinase C (PKC) inhibitors, staurosporine, bisindolylmaleimide I, and H-7 also blocked ANG II-induced stimulation of 2-DG uptake. Indeed, ANG II activated a PKC translocation from the cytosolic to membrane fraction, suggesting a role of PKC. A 23187 (Ca2+ ionophore) increased 2-DG uptake and nifedifine (L-type Ca2+ channel blocker) blocked it. In conclusion, ANG II increased 2-DG uptake by PKC activation via AT1 receptor in mouse ES cells.
Han
Ho Jae
HJ
Department of Veterinary Physiology, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Korea. hjhan@chonnam.ac.kr
Heo
Jung Sun
JS
Lee
Yun Jung
YJ
D000469:Alkaline Phosphatase / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology; D004963:Estrenes / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D051272:Glucose Transporter Type 1; D007093:Imidazoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000187:drug effects; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D050814:Octamer Transcription Factor-3; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D004268:DNA-Binding Proteins; D004963:Estrenes; D051272:Glucose Transporter Type 1; D007093:Imidazoles; D007295:Inositol Phosphates; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D050814:Octamer Transcription Factor-3; D010726:Phosphodiesterase Inhibitors; C494174:Pou5f1 protein, mouse; D011725:Pyridines; D011760:Pyrrolidinones; C495678:Slc2a1 protein, mouse; D014157:Transcription Factors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C073402:PD 123319; D000001:Calcimycin; D003847:Deoxyglucose; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D010738:Type C Phospholipases; D009355:Neomycin; D019808:Losartan; D002118:Calcium