Document Detail

Sodium arsenite exposure inhibits AKT and Stat3 activation, suppresses self-renewal and induces apoptotic death of embryonic stem cells.
MedLine Citation:
PMID:  23143138     Owner:  NLM     Status:  MEDLINE    
Sodium arsenite exposure at concentration >5 μM may induce embryotoxic and teratogenic effects in animal models. Long-term health effects of sodium arsenite from contaminated drinking water may result in different forms of cancer and neurological abnormalities. As cancer development processes seem to be originated in stem cells, we have chosen to examine the effects of sodium arsenite on signaling pathways and the corresponding transcription factors that regulate cell viability and self-renewal in mouse embryonic stem cells (ESC) and mouse neural stem/precursor cells. We demonstrated that the crucial signaling pathway, which was substantially suppressed by sodium arsenite exposure (4 μM) in ESC, was the PI3K-AKT pathway linked with numerous downstream targets that control cell survival and apoptosis. Furthermore, the whole core transcription factor circuitry that control self-renewal of mouse ESC (Stat3-P-Tyr705, Oct4, Sox2 and Nanog) was strongly down-regulated by sodium arsenite (4 μM) exposure. This was followed by G2/M arrest and induction of the mitochondrial apoptotic pathway that might be suppressed by caspase-9 and caspase-3 inhibitors. In contrast to mouse ESC with very low endogenous IL6, mouse neural stem/precursor cells (C17.2 clone immortalized by v-myc) with high endogenous production of IL6 exhibited a strong resistance to cytotoxic effects of sodium arsenite that could be decreased by inhibitory anti-IL6 antibody or Stat3 inhibition. In summary, our data demonstrated suppression of self-renewal and induction of apoptosis in mouse ESC by sodium arsenite exposure, which was further accelerated due to simultaneous inhibition of the protective PI3K-AKT and Stat3-dependent pathways.
Vladimir N Ivanov; Gengyun Wen; Tom K Hei
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  18     ISSN:  1573-675X     ISO Abbreviation:  Apoptosis     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-10-29     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  188-200     Citation Subset:  IM    
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MeSH Terms
Apoptosis / drug effects*
Arsenites / pharmacology*
Cell Survival
Embryonic Stem Cells / drug effects*,  metabolism*
Neural Stem Cells / drug effects
Proto-Oncogene Proteins c-akt / metabolism*
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
Sodium Compounds / pharmacology*
Grant Support
Reg. No./Substance:
0/Arsenites; 0/STAT3 Transcription Factor; 0/Sodium Compounds; 48OVY2OC72/sodium arsenite; EC Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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