Lithium ions Up-regulate mRNAs encoding dense-core vesicle proteins in nerve growth factor-differentiated PC12 cells.
We recently reported that lithium ions induced an up-regulation of cysteine string protein (CSP) gene expression in nerve growth factor (NGF)-differentiated PC12 cells but not in undifferentiated cells. Concomitantly, expression of two other proteins of regulated secretory pathways, synaptophysin (SY) and SNAP-25, was unaffected by lithium. To assess further the specificity of this effect of lithium, we used cDNA arrays. Our data indicate that lithium ions increase the level of mRNA for proteins such as secretogranin II and vesicular monoamine transporter 1 that are preferentially associated with large densecore secretory vesicles (LDCVs) without affecting mRNAs for proteins predominantly affiliated with small synaptic-like vesicles, including the vesicular acetylcholine transporter and SY. This action of lithium is detected in NGF-differentiated PC12 cells but not in undifferentiated cells. These observations suggest that lithium ions modulate the turnover of LDCVs, and this may play a role in mediating the therapeutic action of lithium in manic-depressive illness.
Cordeiro
M L
ML
Department of Molecular and Medical Pharmacology and Crump Institute for Molecular Imaging, School of Medicine, University of California Los Angeles 90095-1770, USA.
Umbach
J A
JA
Gundersen
C B
CB
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002864:Chromogranins; D008094:Lithium / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides; D020411:Oligonucleotide Array Sequence Analysis; D016716:PC12 Cells; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D002864:Chromogranins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D011506:Proteins; D012333:RNA, Messenger; C493461:Slc18a3 protein, rat; D016708:Synaptophysin; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins; D020932:Nerve Growth Factor; D008094:Lithium