Bax-mediated mitochondrial membrane permeabilization after heat treatment is caspase-2 dependent

Nijhuis, E.H.A. and Le Gac, S. and Poot, A.A. and Feijen, J. and Vermes, I. (2008) Bax-mediated mitochondrial membrane permeabilization after heat treatment is caspase-2 dependent. International Journal of Hyperthermia, 24 (4). pp. 357-365. ISSN 0265-6736

PDF
Restricted to UT campus only: Request a copy
364Kb

Abstract:	Heat-induced apoptosis proceeds via mitochondria by permeabilization of the outer mitochondrial membrane (MOMP), resulting in the release of cytochrome c. This essential step is mediated by Bcl-2 family proteins, such as Bax. Recently, caspase-2 was assigned a prominent role in regulating Bax. Therefore, we studied the initiation of heat-induced apoptosis by monitoring Bcl-2 family members and the release of cytochrome c with or without caspase-2 inhibition. Three hematopoietic cell lines (HSB2, HL60 and Kasumi-1) were exposed to heat treatment and/or X-radiation. Expression and localization of Bax and Bcl-2 proteins was investigated by flow cytometry (FCM) and confocal microscopy respectively. Cytochrome c release was measured with FCM as evidence for MOMP. In addition, the role of caspase-2 in heat- and radiation-induced apoptosis was assessed using the specific caspase-2 inhibitor zVDVAD-fmk. Here we present evidence that heat treatment, and not irradiation, increases intracellular Bax protein expression and subsequently stimulates MOMP, resulting in the release of cytochrome c. Furthermore, by selective blocking of caspase-2 using zVDVAD-fmk less Bax was expressed and subsequently a significant decrease in cytochrome c release was observed. In conclusion, heat treatment of hematopoietic cells does require caspase-2 activation for the initiation of Bax-mediated MOMP.
Item Type:	Article
Copyright:	© 2008 Informa
Faculty:	Electrical Engineering, Mathematics and Computer Science (EEMCS) Science and Technology (TNW)
Research Group:	Biomedical and Environmental Sensor systems (BIOS) Biomaterials Science and Technology (BST) Polymer Chemistry and BioMaterials (PBM)
Link to this item:	http://purl.utwente.nl/publications/59876
Official URL:	http://dx.doi.org/10.1080/02656730801944914
Export this item as:	BibTeX EndNote HTML Citation Reference Manager

Show download statistics for this publication

Repository Staff Only: item control page

Metis ID: 254269