2024-03-28T13:37:59Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1293092021-09-22T12:11:55Zcom_10261_128com_10261_1col_10261_381
Oropesa-Ávila, Manuel
Fernández-Vega, Alejandro
Mata, Mario de la
Garrido-Maraver, Juan
Cotán, David
Villanueva Paz, Marina
Delgado Pavón, Ana
Cordero, Mario D.
Alcocer-Gómez, Elísabet
Lavera, I. de
Lema, R.
Zaderenko, Paula
Sánchez-Alcázar, José Antonio
2016-02-22T14:00:21Z
2016-02-22T14:00:21Z
2014
Apoptosis 19(9): 1364-1377 (2014)
http://hdl.handle.net/10261/129309
10.1007/s10495-014-1015-y
http://dx.doi.org/10.13039/501100003751
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100011011
Apoptotic microtubule network (AMN) is organized during apoptosis, forming a cortical structure beneath the plasma membrane which plays a critical role in preserving cell morphology and plasma membrane integrity. The aim of this study was to examine the effect of cold/warming exposure on apoptotic microtubules and plasma membrane integrity during the execution phase of apoptosis. We demonstrated in camptothecin-induced apoptotic H460 cells that cold/warming exposure disorganized apoptotic microtubules and allowed the access of active caspases to the cellular cortex and the cleavage of essential proteins in the preservation of plasma membrane permeability. Cleavage of cellular cortex and plasma membrane proteins, such as ¿-spectrin, paxilin, focal adhesion kinase and calcium ATPase pump (PMCA-4) involved in cell calcium extrusion resulted in increased plasma permeability and calcium overload leading apoptotic cells to secondary necrosis. The essential role of caspase-mediated cleavage in this process was demonstrated because the addition of the pan-caspase inhibitor z-VAD during cold/warming exposure that induces AMN depolymerization avoided the cleavage of cortical and plasma membrane proteins and prevented apoptotic cells to undergo secondary necrosis. Likewise, apoptotic microtubules stabilization by taxol during cold/warming exposure also prevented cellular cortex and plasma membrane protein cleavage and secondary necrosis. Furthermore, microtubules stabilization or caspase inhibition during cold/warming exposure was also critical for proper phosphatidylserine externalization and apoptotic cell clearance by macrophages. These results indicate that cold/warming exposure of apoptotic cells induces secondary necrosis which can be prevented by both, microtubule stabilization or caspase inhibition.
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closedAccess
Apoptotic cells subjected to cold/warming exposure disorganize apoptotic microtubule network and undergo secondary necrosis
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