Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00108504" target="_blank" >RIV/00216224:14110/19:00108504 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/19:00072509
Result on the web
<a href="https://www.hindawi.com/journals/sci/2019/4279481/" target="_blank" >https://www.hindawi.com/journals/sci/2019/4279481/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1155/2019/4279481" target="_blank" >10.1155/2019/4279481</a>
Alternative languages
Result language
angličtina
Original language name
Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin
Original language description
Tumor necrosis factor-related apoptosis-inducing ligand-TRAIL-is a protein operating as a ligand capable of inducing apoptosis particularly in cancerously transformed cells, while normal healthy cells are typically nonresponsive. We have previously demonstrated that pluripotent human embryonic stem cells (hESC) are also refractory to TRAIL, even though they express all canonical components of the death receptor-induced apoptosis pathway. In this study, we have examined a capacity of DNA damage to provoke sensitivity of hESC to TRAIL. The extent of DNA damage, behavior of molecules involved in apoptosis, and response of hESC to TRAIL were investigated. The exposure of hESC to 1 mu M and 2 mu M concentrations of cisplatin have led to the formation of 53BP1 and gamma H2AX foci, indicating the presence of double-strand breaks in DNA, without affecting the expression of proteins contributing to mitochondrial membrane integrity. Interestingly, cisplatin upregulated critical components of the extrinsic apoptotic pathway-initiator caspase 8, effector caspase 3, and the cell death receptors. The observed increase of expression of the extrinsic apoptotic pathway components was sufficient to sensitize hESC to TRAIL-induced apoptosis; immense cell dying accompanied by enhanced PARP cleavage, processing of caspase 8, and full activation of caspase 3 were all observed after the treatment combining cisplatin and TRAIL. Finally, we have demonstrated the central role of caspase 8 in this process, since its downregulation abrogated the sensitizing effect of cisplatin.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Stem Cells International
ISSN
1687-966X
e-ISSN
1687-9678
Volume of the periodical
2019
Issue of the periodical within the volume
JAN 21 2019
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
1-11
UT code for WoS article
000482101000001
EID of the result in the Scopus database
2-s2.0-85065766057