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Blecha 2015 Abstract MiP2015 - Revision history
2024-03-29T10:20:59Z
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Beno Marija at 14:58, 9 November 2017
2017-11-09T14:58:23Z
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Beno Marija
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Beno Marija at 08:32, 8 November 2016
2016-11-08T08:32:39Z
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Beno Marija
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Kandolf Georg at 14:13, 4 September 2015
2015-09-04T14:13:56Z
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Kandolf Georg
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Kandolf Georg at 11:59, 4 September 2015
2015-09-04T11:59:17Z
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Kandolf Georg
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Kandolf Georg at 09:44, 24 August 2015
2015-08-24T09:44:57Z
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<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><del style="font-weight: bold; text-decoration: none;">== References and acknowledgements ==</del></div></td><td colspan="2"></td></tr>
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Kandolf Georg
https://wiki.oroboros.at/index.php?title=Blecha_2015_Abstract_MiP2015&diff=96669&oldid=prev
Kandolf Georg at 09:44, 24 August 2015
2015-08-24T09:44:47Z
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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>|abstract=Mitochondrial electron transport chain (ETC) drives ATP production and is the major source of reactive oxygen species (ROS). We have previously shown that mitochondrially targeted vitamin E succinate (MitoVES) induces cell death by inhibiting complex II of ETC, leading to considerable ROS production. In addition, MitoVES selectively eliminates proliferating but not quiescent (confluent) endothelial cells (ECs) and suppresses tumorigenic angiogenesis ''in vivo''. This suggests that modulation of ETC activity in proliferating and quiescent cells might have different outcomes with respect to cell death induction. To investigate the role of ROS generation and inhibition of ATP production (ETC inhibition may result in both), we cultured ECs in low (1 g/L) and high glucose (4.5 g/L) that promotes and suppresses mitochondrial respiration/ATP production, respectively. We exposed these cells to agents that induce ROS without ETC inhibition (phenethylisothiocyanate - PEITC, and hydrogen peroxide), inhibit ETC (rotenone, antimycin A) or directly interfere with mitochondrial ATP production (FCCP, oligomycin). Interestingly, PEITC and hydrogen peroxide induced cell death and ROS preferentially in proliferating cells irrespective of cell culture conditions. In contrast, treatment with the other compounds resulted in more cell death in proliferating than in quiescent cells when glucose was high, but this pattern was reversed when glucose was low. In addition, ROS generation only correlated with cell death induction in high glucose. Respiration measurements showed that cells grown in high glucose slightly reduced, and cells grown in low glucose significantly increased respiration on entering the quiescence state. This occurred despite the fact that ETC was primed for high activity in quiescent cells irrespective of glucose concentration, as evidenced by elevated expression of protein subunits and increased enzymatic activity of ETC complexes as well as enhanced supercomplex assembly. These data suggest that in low glucose interference with ETC activity is a major factor for cell death induction, whereas in high glucose the level of ROS generation becomes dominant. We therefore propose that ETC inhibition differentially affects proliferating and quiescent cells and might be the key determinant of proliferation-responsive cell death sensitivity. Experiments to confirm this scenario are ongoing.</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=Mitochondrial electron transport chain (ETC) drives ATP production and is the major source of reactive oxygen species (ROS). We have previously shown that mitochondrially targeted vitamin E succinate (MitoVES) induces cell death by inhibiting complex II of ETC, leading to considerable ROS production. In addition, MitoVES selectively eliminates proliferating but not quiescent (confluent) endothelial cells (ECs) and suppresses tumorigenic angiogenesis ''in vivo''. This suggests that modulation of ETC activity in proliferating and quiescent cells might have different outcomes with respect to cell death induction. To investigate the role of ROS generation and inhibition of ATP production (ETC inhibition may result in both), we cultured ECs in low (1 g/L) and high glucose (4.5 g/L) that promotes and suppresses mitochondrial respiration/ATP production, respectively. We exposed these cells to agents that induce ROS without ETC inhibition (phenethylisothiocyanate - PEITC, and hydrogen peroxide), inhibit ETC (rotenone, antimycin A) or directly interfere with mitochondrial ATP production (FCCP, oligomycin). Interestingly, PEITC and hydrogen peroxide induced cell death and ROS preferentially in proliferating cells irrespective of cell culture conditions. In contrast, treatment with the other compounds resulted in more cell death in proliferating than in quiescent cells when glucose was high, but this pattern was reversed when glucose was low. In addition, ROS generation only correlated with cell death induction in high glucose. Respiration measurements showed that cells grown in high glucose slightly reduced, and cells grown in low glucose significantly increased respiration on entering the quiescence state. This occurred despite the fact that ETC was primed for high activity in quiescent cells irrespective of glucose concentration, as evidenced by elevated expression of protein subunits and increased enzymatic activity of ETC complexes as well as enhanced supercomplex assembly. These data suggest that in low glucose interference with ETC activity is a major factor for cell death induction, whereas in high glucose the level of ROS generation becomes dominant. We therefore propose that ETC inhibition differentially affects proliferating and quiescent cells and might be the key determinant of proliferation-responsive cell death sensitivity. Experiments to confirm this scenario are ongoing.</div></td></tr>
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</table>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Blecha_2015_Abstract_MiP2015&diff=96665&oldid=prev
Kandolf Georg at 09:42, 24 August 2015
2015-08-24T09:42:36Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">← Older revision</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:42, 24 August 2015</td>
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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>{{Abstract</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</div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|title=Modulation of mitochondrial electron transport chain activity differentially regulates cell death in proliferating and quiescent cells.</ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|authors=Blecha J, Neuzil J, Rohlena J</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>|year=2015</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>|year=2015</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>|event=MiP2015</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>|event=MiP2015</div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|abstract=Mitochondrial electron transport chain (ETC) drives ATP production and is the major source of reactive oxygen species (ROS). We have previously shown that mitochondrially targeted vitamin E succinate (MitoVES) induces cell death by inhibiting complex II of ETC, leading to considerable ROS production. In addition, MitoVES selectively eliminates proliferating but not quiescent (confluent) endothelial cells (ECs) and suppresses tumorigenic angiogenesis ''in vivo''. This suggests that modulation of ETC activity in proliferating and quiescent cells might have different outcomes with respect to cell death induction. To investigate the role of ROS generation and inhibition of ATP production (ETC inhibition may result in both), we cultured ECs in low (1 g/L) and high glucose (4.5 g/L) that promotes and suppresses mitochondrial respiration/ATP production, respectively. We exposed these cells to agents that induce ROS without ETC inhibition (phenethylisothiocyanate - PEITC, and hydrogen peroxide), inhibit ETC (rotenone, antimycin A) or directly interfere with mitochondrial ATP production (FCCP, oligomycin). Interestingly, PEITC and hydrogen peroxide induced cell death and ROS preferentially in proliferating cells irrespective of cell culture conditions. In contrast, treatment with the other compounds resulted in more cell death in proliferating than in quiescent cells when glucose was high, but this pattern was reversed when glucose was low. In addition, ROS generation only correlated with cell death induction in high glucose. Respiration measurements showed that cells grown in high glucose slightly reduced, and cells grown in low glucose significantly increased respiration on entering the quiescence state. This occurred despite the fact that ETC was primed for high activity in quiescent cells irrespective of glucose concentration, as evidenced by elevated expression of protein subunits and increased enzymatic activity of ETC complexes as well as enhanced supercomplex assembly. These data suggest that in low glucose interference with ETC activity is a major factor for cell death induction, whereas in high glucose the level of ROS generation becomes dominant. We therefore propose that ETC inhibition differentially affects proliferating and quiescent cells and might be the key determinant of proliferation-responsive cell death sensitivity. Experiments to confirm this scenario are ongoing.</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;"><br/></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;"><br/></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|mipnetlab=CZ Prague Neuzil J, AU Queensland Neuzil J</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>}}</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>}}</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>{{Labeling</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>{{Labeling</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>|additional=MiP2015}}</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><ins style="font-weight: bold; text-decoration: none;">|area=Respiration</ins></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> </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><ins style="font-weight: bold; text-decoration: none;">|injuries=Cell death, Oxidative stress;RONS</ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|couplingstates=LEAK, ETS</ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|substratestates=ROX</ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">|instruments=Oxygraph-2k</ins></div></td></tr>
<tr><td colspan="2"></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>|additional=MiP2015</div></td></tr>
<tr><td colspan="2"></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>}}</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>== Affiliations ==</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>== Affiliations ==</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> </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><ins style="font-weight: bold; text-decoration: none;">1-Inst Biotechnology, Czech Academy of Sc, Prague, Czech Republic;</ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">2-Fac Science, Charles Univ Prague, Czech Republic;</ins></div></td></tr>
<tr><td colspan="2"></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><ins style="font-weight: bold; text-decoration: none;">3-School Medical Sc, Griffith Univ, Southport, Queensland, Australia. - </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;"><br/></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;"><br/></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>== References and acknowledgements ==</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>== References and acknowledgements ==</div></td></tr>
</table>
Kandolf Georg
https://wiki.oroboros.at/index.php?title=Blecha_2015_Abstract_MiP2015&diff=96661&oldid=prev
Kandolf Georg: Created page with "{{Abstract |year=2015 |event=MiP2015 }} {{Labeling |additional=MiP2015}} == Affiliations == == References and acknowledgements =="
2015-08-24T09:22:53Z
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== Affiliations ==<br />
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== References and acknowledgements ==</div>
Kandolf Georg