Galectin-1 upregulates glucose transporter-1 expression level via protein kinase C, phosphoinositol-3 kinase, and mammalian target of rapamycin pathways in mouse embryonic stem cells.
Although galectin-1 is expressed in various stem cells, our understanding of the functional roles of galectin-1 in embryonic stem (ES) cells is still fragmentary and incomplete. Thus, this study investigated the effect of galectin-1 on the 2-deoxyglucose (2-DG) uptake and its related signal cascades. Galectin-1 significantly increased 2-deoxyglucose uptake time- and dose-dependently. In addition, galectin-1-induced 2-deoxyglucose uptake was inhibited by glucose transporter-1 siRNA. Moreover, galectin-1 increased glucose transporter-1 mRNA and protein expression levels, which were inhibited by a disruption in transcription by actinomycin D and translation by the cycloheximide. Subsequently, the galectin-1-induced 2-deoxyglucose uptake was attenuated by these inhibitors. In investigation of signal transduction involved in this process, galectin-1 increased intracellular Ca2+ concentration and the protein kinase C activation, which induced extracellular signal regulated kinase1/2 phosphorylation. On the other hand, phosphoinositol-3-kinase/Akt activated by galectin-1 was not involved in extracellular signal regulated kinase1/2 pathway. Moreover, mammalian target of rapamycin signal pathway was stimulated in response to galectin-1. Finally, galectin-1-induced increase of glucose transporter-1 expression and 2-deoxyglucose uptake were inhibited by blocking of Ca2+/protein kinase C/extracellular signal regulated kinase1/2, phosphoinositol-3-kinase/Akt, and mammalian target of rapamycin pathways. In conclusion, galectin-1 upregulates glucose uptake through Ca2+/protein kinase C/extracellular signal regulated kinase1/2, phosphoinositol-3-kinase/Akt, and mammalian target of rapamycin pathways in mouse ES cells.
Lee
Min Young
MY
Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Han
Ho Jae
HJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D003847:Deoxyglucose / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D039642:Eukaryotic Initiation Factors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008301:Maleimides / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003847:Deoxyglucose; D004791:Enzyme Inhibitors; D039642:Eukaryotic Initiation Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D037483:Galectin 1; D051272:Glucose Transporter Type 1; D007211:Indoles; D008301:Maleimides; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011493:Protein Kinase C; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D050796:STAT3 Transcription Factor; D058570:TOR Serine-Threonine Kinases; C499527:Eif4ebp1 protein, mouse; C495678:Slc2a1 protein, mouse; C494087:Stat3 protein, mouse; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C088060:bisindolylmaleimide