Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways
<p>As we previously demonstrated in human hepatocellular carcinoma (HepG2) cells, ethanol at low concentration triggers the Fas apoptotic pathway. However, its role in other intracellular signaling pathways remains unknown. Therefore, the aim of the present study was to evaluate the role of lo...
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| Format: | Article |
| Language: | English |
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Ivyspring International Publisher
2006-01-01
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| Series: | International Journal of Medical Sciences |
| Online Access: | http://www.medsci.org/v03p0160.htm |
| _version_ | 1818291742386946048 |
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| author | Francisco Castaneda, Sigrid Rosin-Steiner |
| author_facet | Francisco Castaneda, Sigrid Rosin-Steiner |
| author_sort | Francisco Castaneda, Sigrid Rosin-Steiner |
| collection | DOAJ |
| description | <p>As we previously demonstrated in human hepatocellular carcinoma (HepG2) cells, ethanol at low concentration triggers the Fas apoptotic pathway. However, its role in other intracellular signaling pathways remains unknown. Therefore, the aim of the present study was to evaluate the role of low concentration of ethanol on different intracellular signaling pathways. For this purpose, HepG2 cells were treated with 1 mM ethanol for 10 min and the phosphorylation state of protein kinases was determined. In addition, the mRNA levels of transcription factors and genes associated with the Fas apoptotic pathway were determined. Our data demonstrated that ethanol-induced phosphorylation of protein kinases modulates both anti-apoptotic and pro-apoptotic mechanisms in HepG2 cells. Pro-apoptosis resulted mainly from the strong inhibition of the G-protein couple receptor signaling pathway. Moreover, the signal transduction initiated by ethanol-induced protein kinases phosphorylation lead to increased expression of the transcription factors with subsequent expression of genes associated with the Fas apoptotic pathway (Fas receptor, Fas ligand, FADD and caspase 8). These results indicate that low concentration of ethanol exert their effect by predominant activation of pro-apoptotic events that can be divided in two phases. An early phase characterized by a rapid transient effect on protein kinases phosphorylation, after 10 min exposure, with subsequent increased expression of transcription factors for up to 6 hr. This early phase is followed by a second phase associated with increased gene expression that began after 6 hr and persisted for more than 24 hr. This information provided a novel insight into the mechanisms of action of ethanol (1mM) in human hepatocellular carcinoma cells.</p> |
| first_indexed | 2024-12-13T02:48:54Z |
| format | Article |
| id | doaj.art-59737fdd92b946bab9be1b4a7d961f48 |
| institution | Directory Open Access Journal |
| issn | 1449-1907 |
| language | English |
| last_indexed | 2024-12-13T02:48:54Z |
| publishDate | 2006-01-01 |
| publisher | Ivyspring International Publisher |
| record_format | Article |
| series | International Journal of Medical Sciences |
| spelling | doaj.art-59737fdd92b946bab9be1b4a7d961f482022-12-22T00:02:07ZengIvyspring International PublisherInternational Journal of Medical Sciences1449-19072006-01-0134160167Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathwaysFrancisco Castaneda, Sigrid Rosin-Steiner<p>As we previously demonstrated in human hepatocellular carcinoma (HepG2) cells, ethanol at low concentration triggers the Fas apoptotic pathway. However, its role in other intracellular signaling pathways remains unknown. Therefore, the aim of the present study was to evaluate the role of low concentration of ethanol on different intracellular signaling pathways. For this purpose, HepG2 cells were treated with 1 mM ethanol for 10 min and the phosphorylation state of protein kinases was determined. In addition, the mRNA levels of transcription factors and genes associated with the Fas apoptotic pathway were determined. Our data demonstrated that ethanol-induced phosphorylation of protein kinases modulates both anti-apoptotic and pro-apoptotic mechanisms in HepG2 cells. Pro-apoptosis resulted mainly from the strong inhibition of the G-protein couple receptor signaling pathway. Moreover, the signal transduction initiated by ethanol-induced protein kinases phosphorylation lead to increased expression of the transcription factors with subsequent expression of genes associated with the Fas apoptotic pathway (Fas receptor, Fas ligand, FADD and caspase 8). These results indicate that low concentration of ethanol exert their effect by predominant activation of pro-apoptotic events that can be divided in two phases. An early phase characterized by a rapid transient effect on protein kinases phosphorylation, after 10 min exposure, with subsequent increased expression of transcription factors for up to 6 hr. This early phase is followed by a second phase associated with increased gene expression that began after 6 hr and persisted for more than 24 hr. This information provided a novel insight into the mechanisms of action of ethanol (1mM) in human hepatocellular carcinoma cells.</p>http://www.medsci.org/v03p0160.htm |
| spellingShingle | Francisco Castaneda, Sigrid Rosin-Steiner Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways International Journal of Medical Sciences |
| title | Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways |
| title_full | Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways |
| title_fullStr | Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways |
| title_full_unstemmed | Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways |
| title_short | Low concentration of ethanol induce apoptosis in HepG2 cells: role of various signal transduction pathways |
| title_sort | low concentration of ethanol induce apoptosis in hepg2 cells role of various signal transduction pathways |
| url | http://www.medsci.org/v03p0160.htm |
| work_keys_str_mv | AT franciscocastanedasigridrosinsteiner lowconcentrationofethanolinduceapoptosisinhepg2cellsroleofvarioussignaltransductionpathways |