Elevation of somatic Ca2+ upregulates genes Nr4a1 and Egr2, but not Bdnf and Arc.
Blockage of Ca2+ uptake with thapsigargin, a specific antagonist of sarco/endoplasmic reticulum Ca2+-ATPase pumps, causes an increase of somatic Ca2+, with negligible changes of Ca2+ levels in dendrites. Treatment with thapsigargin in the presence of blockers of NMDA (N-methyl-D-aspartic acid) receptors upregulates some activity-dependent genes (Egr2 and Nr4a1), leaving unaltered the expression level of other activity-dependent genes (Bdnf and Arc). These results show that the elevation of somatic Ca2+ can initiate transcription of specific genes, independently of activation of NMDA receptors, but that transcription of other genes is not initiated by a simple elevation of intracellular Ca2+.
International School for Advanced Studies, Trieste, Italy. pinato@sissa.it
Giulietta
G
Pinato
Silvia
S
Pegoraro
Marco
M
Visentini
Maria Elisabetta
ME
Ruaro
Vincent
V
Torre
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000187:drug effects / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497328:Egr2 protein, rat; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011987:Receptors, Steroid; C092069:activity regulated cytoskeletal-associated protein; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium