Document Detail


Effect of ionic stress on apoptosis and the expression of TRPM2 in human olfactory neuroepithelial-derived progenitors.
MedLine Citation:
PMID:  20799912     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
OBJECTIVES: Disturbed ion homeostasis and apoptosis have been implicated in the pathophysiology of bipolar disorder (BD). TRPM2, a nonselective cation channel, is involved in apoptosis and is possibly linked with BD. In this study, monensin, a sodium ionophore, was used to model the increase [Na(+)](in) and [Ca(2+)](in) seen in BD patients.
METHODS: Human olfactory neuroepithelial-derived progenitors (ONP), which possess neuronal markers, were utilized to investigate the effects of monensin on apoptosis and the response of TRPM2, and the effects of lithium on the cellular response to monensin. Monensin treatment for 6 h activated caspase-3, -7 and poly(ADP-ribose) polymerase (PARP), inducing apoptosis.
RESULTS: [Na(+)](in) increased to twice the basal level and reached steady state after 2 h of 10(-6) M monensin treatment, while [Ca(2+)](in) rose after 6 h of the treatment. Monensin treatment for 24 h decreased expression of the long form of TRPM2, and increased expression of the short form. Lithium (1 mM) pretreatment reduced the [Na(+)](in) and [Ca(2+)](in) elevation caused by monensin, down-regulated the levels of caspase-3, -7 and PARP, and reduced expression of TRPM2.
CONCLUSIONS: Our findings suggest that the elevation of [Na(+)](in) and [Ca(2+)](in) induced ONP apoptosis and altered the expression of TRPM2. Lithium pretreatment attenuated the apoptosis induced by ionic stress.
Authors:
Yonglin Gao; Zhenmin Lei; Chengliang Lu; Fred J Roisen; Rif S El-Mallakh
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-30
Journal Detail:
Title:  The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry     Volume:  11     ISSN:  1814-1412     ISO Abbreviation:  World J. Biol. Psychiatry     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101120023     Medline TA:  World J Biol Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  972-84     Citation Subset:  IM    
Affiliation:
Department of Psychiatry and Behavioral Sciences, University of Louisville, School of Medicine, Louisville, KY 40292, USA.
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