https://wiki.oroboros.at/index.php?title=Rohde_2017_Cell_Death_Differ&feed=atom&action=historyRohde 2017 Cell Death Differ - Revision history2024-03-28T17:31:35ZRevision history for this page on the wikiMediaWiki 1.36.1https://wiki.oroboros.at/index.php?title=Rohde_2017_Cell_Death_Differ&diff=191589&oldid=prevGnaiger Erich at 16:33, 31 January 20202020-01-31T16:33:49Z<p></p>
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</table>Gnaiger Erichhttps://wiki.oroboros.at/index.php?title=Rohde_2017_Cell_Death_Differ&diff=163090&oldid=prevPlangger Mario at 11:30, 26 September 20182018-09-26T11:30:29Z<p></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|authors=Rohde K, Kleinesudeik L, Roesler S, Loewe O, Heidler J, Schroeder K, Wittig I, Droese S, Fulda S</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|authors=Rohde K, Kleinesudeik L, Roesler S, Loewe O, Heidler J, Schroeder K, Wittig I, Droese S, Fulda S</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|year=<del style="font-weight: bold; text-decoration: none;">2018</del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|year=<ins style="font-weight: bold; text-decoration: none;">2017</ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=Cell Death Differ</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=Cell Death Differ</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Necroptosis is a form of programmed cell death that critically depends on RIP3 and MLKL. However, the contribution of mitochondria to necroptosis is still poorly understood. In the present study, we discovered that mitochondrial perturbations play a critical role in Smac mimetic/Dexamethasone (Dexa)-induced necroptosis independently of death receptor ligands. We demonstrate that the Smac mimetic BV6 and Dexa cooperate to trigger necroptotic cell death in acute lymphoblastic leukemia (ALL) cells that are deficient in caspase activation due to absent caspase-8 expression or pharmacological inhibition by the caspase inhibitor zVAD.fmk, since genetic silencing or pharmacological inhibition of RIP3 or MLKL significantly rescue BV6/Dexa-induced necroptosis. In addition, RIP3 or MLKL knockout mouse embryonic fibroblasts (MEFs) are protected from BV6/Dexa/zVAD.fmk-induced cell death. In contrast, antagonistic antibodies against the death receptor ligands TNFα, TRAIL or CD95 ligand fail to rescue BV6/Dexa-triggered cell death. Kinetic studies revealed that prior to cell death BV6/Dexa treatment causes hyperpolarization of the mitochondrial membrane potential (MMP) followed by loss of MMP, reactive oxygen species (ROS) production, Bak activation and disruption of mitochondrial respiration. Importantly, knockdown of Bak significantly reduces BV6/Dexa-induced loss of MMP and delays cell death, but not ROS production, whereas ROS scavengers attenuate Bak activation, indicating that ROS production occurs upstream of BV6/Dexa-mediated Bak activation. Consistently, BV6/Dexa treatment causes oxidative thiol modifications of Bak protein. Intriguingly, knockdown or knockout of RIP3 or MLKL protect ALL cells or MEFs from BV6/Dexa-induced ROS production, Bak activation, drop of MMP and disruption of mitochondrial respiration, demonstrating that these mitochondrial events depend on RIP3 and MLKL. Thus, mitochondria might serve as an amplification step in BV6/Dexa-induced necroptosis. These findings provide new insights into the role of mitochondrial dysfunctions during necroptosis and have important implications for the development of novel treatment approaches to overcome apoptosis resistance in ALL.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Necroptosis is a form of programmed cell death that critically depends on RIP3 and MLKL. However, the contribution of mitochondria to necroptosis is still poorly understood. In the present study, we discovered that mitochondrial perturbations play a critical role in Smac mimetic/Dexamethasone (Dexa)-induced necroptosis independently of death receptor ligands. We demonstrate that the Smac mimetic BV6 and Dexa cooperate to trigger necroptotic cell death in acute lymphoblastic leukemia (ALL) cells that are deficient in caspase activation due to absent caspase-8 expression or pharmacological inhibition by the caspase inhibitor zVAD.fmk, since genetic silencing or pharmacological inhibition of RIP3 or MLKL significantly rescue BV6/Dexa-induced necroptosis. In addition, RIP3 or MLKL knockout mouse embryonic fibroblasts (MEFs) are protected from BV6/Dexa/zVAD.fmk-induced cell death. In contrast, antagonistic antibodies against the death receptor ligands TNFα, TRAIL or CD95 ligand fail to rescue BV6/Dexa-triggered cell death. Kinetic studies revealed that prior to cell death BV6/Dexa treatment causes hyperpolarization of the mitochondrial membrane potential (MMP) followed by loss of MMP, reactive oxygen species (ROS) production, Bak activation and disruption of mitochondrial respiration. Importantly, knockdown of Bak significantly reduces BV6/Dexa-induced loss of MMP and delays cell death, but not ROS production, whereas ROS scavengers attenuate Bak activation, indicating that ROS production occurs upstream of BV6/Dexa-mediated Bak activation. Consistently, BV6/Dexa treatment causes oxidative thiol modifications of Bak protein. Intriguingly, knockdown or knockout of RIP3 or MLKL protect ALL cells or MEFs from BV6/Dexa-induced ROS production, Bak activation, drop of MMP and disruption of mitochondrial respiration, demonstrating that these mitochondrial events depend on RIP3 and MLKL. Thus, mitochondria might serve as an amplification step in BV6/Dexa-induced necroptosis. These findings provide new insights into the role of mitochondrial dysfunctions during necroptosis and have important implications for the development of novel treatment approaches to overcome apoptosis resistance in ALL.</div></td></tr>
</table>Plangger Mariohttps://wiki.oroboros.at/index.php?title=Rohde_2017_Cell_Death_Differ&diff=163089&oldid=prevPlangger Mario at 11:30, 26 September 20182018-09-26T11:30:08Z<p></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/27834956 PMID: 27834956 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/27834956 PMID: 27834956 Open Access]</div></td></tr>
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</table>Plangger Mariohttps://wiki.oroboros.at/index.php?title=Rohde_2017_Cell_Death_Differ&diff=163088&oldid=prevPlangger Mario: Plangger Mario moved page Rohde 2018 Cell Death Differ to Rohde 2017 Cell Death Differ without leaving a redirect2018-09-26T11:29:51Z<p>Plangger Mario moved page <a href="/index.php?title=Rohde_2018_Cell_Death_Differ&action=edit&redlink=1" class="new" title="Rohde 2018 Cell Death Differ (page does not exist)">Rohde 2018 Cell Death Differ</a> to <a href="/index.php/Rohde_2017_Cell_Death_Differ" title="Rohde 2017 Cell Death Differ">Rohde 2017 Cell Death Differ</a> without leaving a redirect</p>
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<td colspan="1" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 11:29, 26 September 2018</td>
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</td></tr></table>Plangger Mariohttps://wiki.oroboros.at/index.php?title=Rohde_2017_Cell_Death_Differ&diff=163086&oldid=prevPlangger Mario: Created page with "{{Publication |title=Rohde K, Kleinesudeik L, Roesler S, Löwe O, Heidler J, Schröder K, Wittig I, Dröse S, Fulda S (2018) A Bak-dependent mitochondrial amplification step c..."2018-09-26T11:23:16Z<p>Created page with "{{Publication |title=Rohde K, Kleinesudeik L, Roesler S, Löwe O, Heidler J, Schröder K, Wittig I, Dröse S, Fulda S (2018) A Bak-dependent mitochondrial amplification step c..."</p>
<p><b>New page</b></p><div>{{Publication<br />
|title=Rohde K, Kleinesudeik L, Roesler S, Löwe O, Heidler J, Schröder K, Wittig I, Dröse S, Fulda S (2018) A Bak-dependent mitochondrial amplification step contributes to Smac mimetic/glucocorticoid-induced necroptosis. Cell Death Differ 24:83-97.<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/27834956 PMID: 27834956 Open Access]<br />
|authors=Rohde K, Kleinesudeik L, Roesler S, Loewe O, Heidler J, Schroeder K, Wittig I, Droese S, Fulda S<br />
|year=2018<br />
|journal=Cell Death Differ<br />
|abstract=Necroptosis is a form of programmed cell death that critically depends on RIP3 and MLKL. However, the contribution of mitochondria to necroptosis is still poorly understood. In the present study, we discovered that mitochondrial perturbations play a critical role in Smac mimetic/Dexamethasone (Dexa)-induced necroptosis independently of death receptor ligands. We demonstrate that the Smac mimetic BV6 and Dexa cooperate to trigger necroptotic cell death in acute lymphoblastic leukemia (ALL) cells that are deficient in caspase activation due to absent caspase-8 expression or pharmacological inhibition by the caspase inhibitor zVAD.fmk, since genetic silencing or pharmacological inhibition of RIP3 or MLKL significantly rescue BV6/Dexa-induced necroptosis. In addition, RIP3 or MLKL knockout mouse embryonic fibroblasts (MEFs) are protected from BV6/Dexa/zVAD.fmk-induced cell death. In contrast, antagonistic antibodies against the death receptor ligands TNFα, TRAIL or CD95 ligand fail to rescue BV6/Dexa-triggered cell death. Kinetic studies revealed that prior to cell death BV6/Dexa treatment causes hyperpolarization of the mitochondrial membrane potential (MMP) followed by loss of MMP, reactive oxygen species (ROS) production, Bak activation and disruption of mitochondrial respiration. Importantly, knockdown of Bak significantly reduces BV6/Dexa-induced loss of MMP and delays cell death, but not ROS production, whereas ROS scavengers attenuate Bak activation, indicating that ROS production occurs upstream of BV6/Dexa-mediated Bak activation. Consistently, BV6/Dexa treatment causes oxidative thiol modifications of Bak protein. Intriguingly, knockdown or knockout of RIP3 or MLKL protect ALL cells or MEFs from BV6/Dexa-induced ROS production, Bak activation, drop of MMP and disruption of mitochondrial respiration, demonstrating that these mitochondrial events depend on RIP3 and MLKL. Thus, mitochondria might serve as an amplification step in BV6/Dexa-induced necroptosis. These findings provide new insights into the role of mitochondrial dysfunctions during necroptosis and have important implications for the development of novel treatment approaches to overcome apoptosis resistance in ALL.<br />
|editor=[[Plangger M]],<br />
|mipnetlab=DE Frankfurt Droese S<br />
}}<br />
{{Labeling<br />
|area=Respiration, Genetic knockout;overexpression<br />
|diseases=Cancer<br />
|injuries=Cell death<br />
|organism=Mouse<br />
|tissues=Fibroblast<br />
|preparations=Intact cells<br />
|couplingstates=LEAK, ROUTINE, ET<br />
|pathways=CIV, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-09,<br />
}}</div>Plangger Mario