title: Estrogen suppresses the impact of glucose deprivation on astrocytic calcium levels and signaling independently of the nuclear estrogen receptor.
abstract: Glucose deprivation of astrocytes results in an elevation of cytosolic calcium concentration ([Ca2+]i) [Kahlert, S., Reiser, G., 2000. Requirement of glycolytic and mitochondrial energy supply for loading of Ca2+ stores and InsP3-mediated Ca2+ signaling in rat hippocampus astrocytes. J. Neurosci. Res. 61, 409-420; Silver, I.A., Deas, J., Erecinska, M., 1997. Ion homeostasis in brain cells: differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience 78, 589-601] equivalent to an impairment of astrocytic energy metabolism and function. Superfusion of fura-2 loaded primary cortical astrocytes with glucose-free solution triggered a slow and progressive, 56-fold increase of the [Ca2+]i from 60 nM up to 3.3 microM within 2 h. Re-addition of glucose led to a rapid drop of [Ca2+]i, yet [Ca2+]i did not fully recover to the low levels recorded prior to glucose deprivation and, moreover, astrocytic Ca2+ signaling was impaired: adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) were no longer able to trigger a transient Ca2+ response as recorded in controls. 17beta-estradiol protected astrocytes from the glucose deprivation-induced [Ca2+]i increase and the impaired signaling independently of the nuclear estrogen receptor, as the antiestrogen tamoxifen and the protein synthesis inhibitor cycloheximide did not impede the protective effect of 17beta-estradiol.
authors.affiliation: Emmy Noether Research Group Brain Energy Metabolism, Cellular Neurosciences, Max Delbrueck Center for Molecular Medicine, Robert-Roessle-Str. 10, 13092 Berlin, Germany. arnold@mdc-berlin.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Arnold
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D007003:Hypoglycemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium; D014544:Uridine Triphosphate