Role of calcium in the activation of erp72 and heme oxygenase-1 expression on depletion of endoplasmic reticulum calcium stores in rat neuronal cell culture.
Endoplasmic reticulum (ER) calcium pool depletion was induced by 30 min exposure of primary neuronal cells to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase. Twelve hours later, erp72 and heme oxygenase-1 (HO-1) mRNA levels were quantified by PCR. Protein synthesis was also measured. Transient Tg exposure of neurons induced a marked rise in mRNA levels (7-fold and a 21-fold increase in erp72 and HO-1 mRNA levels; P < 0.001). Loading of neurons with the calcium chelator 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'-tetra(acetoxymethyl)ester (BAPTA-AM) prior to thapsigargin treatment had only a minor effect on the Tg-induced rise in gene expression. This small inhibitory effect may result from the severe suppression of protein synthesis caused by BAPTA-AM. The results suggest that the increase in stress gene expression induced by exposure of neurons to Tg is triggered by a decrease in ER calcium activity and not by the corresponding increase in cytoplasmic calcium activity.
Linden
T
T
Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Köln, Germany.
Doutheil
J
J
Paschen
W
W
D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002451:Cell Compartmentation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002614:Chelating Agents / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; C062477:endoplasmic reticulum glycoprotein p72; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019284:Thapsigargin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D000252:Calcium-Transporting ATPases; D002118:Calcium