Cell-type specific regulation of calreticulin and Bcl-2 expression by mood stabilizer drugs.
Recent studies in rat brain and cell cultures have demonstrated that expression of the peptide-folding chaperone protein calreticulin is increased by valproate treatment, while the anti-apoptotic Bcl-2 is increased by both lithium and valproate. We asked whether a similar pattern of regulation by these drugs is evident in human neuronal and glial cells. One-week treatment with 1 mM valproate induced a significant (90%) increase in calreticulin mRNA and protein levels in SVG, a glial cell line, but reduced its mRNA levels by 38% in hNT neuronal cells. Valproate also markedly increased Bcl-2 mRNA levels by 260%, but only in hNT neurons. In contrast, lithium had no significant effect in either cell type. Valproate-induced increases in calreticulin may therefore show glial specificity in humans, while changes in Bcl-2 levels may be neuron specific. These results highlight the cell model dependence of outcomes in molecular studies of mood stabilizer effects and the need for caution in interpreting findings in model systems.
Corson
Timothy W
TW
Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health, Clarke Site, Toronto, Ontario, Canada M5T 1R8.
Woo
Karen K
KK
Li
Peter P
PP
Warsh
Jerry J
JJ
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D018692:Antimanic Agents / Q000494:pharmacology*; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D002210:Caprylates / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D008094:Lithium / Q000494:pharmacology; D009457:Neuroglia; D009474:Neurons; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014635:Valproic Acid / Q000494:pharmacology*
D000959:Antihypertensive Agents; D018692:Antimanic Agents; D037282:Calreticulin; D002210:Caprylates; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014635:Valproic Acid; D008094:Lithium; C031492:octanoic acid