Calcium flux in neuroblastoma cells is a coupling mechanism between non-genomic and genomic modes of estrogens.
Estrogens have been demonstrated to rapidly modulate calcium levels in a variety of cell types. However, the significance of estrogen-mediated calcium flux in neuronal cells is largely unknown. The relative importance of intra- and extracellular sources of calcium in estrogenic effects on neurons is also not well understood. Previously, we have demonstrated that membrane-limited estrogens, such as E-BSA given before an administration of a 2-hour pulse of 17beta-estradiol (E2), can potentiate the transcription mediated by E2 from a consensus estrogen response element (ERE)-driven reporter gene. Inhibitors to signal transduction cascades given along with E-BSA or E2 demonstrated that calcium flux is important for E-BSA-mediated potentiation of transcription in a transiently transfected neuroblastoma cell line. In this report, we have used inhibitors to different voltage-gated calcium channels (VGCCs) and to intracellular store receptors along with E-BSA in the first pulse or with E2 in the second pulse to investigate the relative importance of these channels to estrogen-mediated transcription. Neither L- nor P-type VGCCs seem to play a role in estrogen action in these cells; while N-type VGCCs are important in both the non-genomic and genomic modes of estrogen action. Specific inhibitors also showed that the ryanodine receptor and the inositol trisphosphate receptor are important to E-BSA-mediated transcriptional potentiation. This report provides evidence that while intracellular stores of calcium are required to couple non-genomic actions of estrogen initiated at the membrane to transcription in the nucleus, extracellular sources of calcium are also important in both non-genomic and genomic actions of estrogens.
Zhao
Xing
X
Department of Biology, Pennsylvania State University, University Park, PA 16802 , USA.
MacBride
Megan M
MM
Peterson
Blake R
BR
Pfaff
Donald W
DW
Vasudevan
Nandini
N
D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D004967:Estrogens / Q000378:metabolism*; D045604:Extracellular Fluid / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000502:physiology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004967:Estrogens; D019837:Ryanodine Receptor Calcium Release Channel