Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo2L induces apoptosis in a wide variety of cancer and transformed cells. Activation of BID, a “BH3-domain-only” Bcl-2 family member, triggers the oligomerization of proapoptotic family members Bak or Bax, resulting in the release of mitochondrial proteins to cytosol. In this study, we have shown the importance of Bax and Bak in ...

PURPOSE To investigate the effects of benzalkonium chloride (BAK) on the human reconstituted corneal epithelial model (HCE) and to optimize the operating potential of this model in the field of ophthalmic toxicology. METHODS The HCEs were treated with 0.001% to 0.5% BAK for 24 hours followed or not by a 24-hour postincubation period. To complete the histologic analysis, the authors designed a...

The function Bax and/or Bak in constituting a gateway for mitochondrial apoptosis in response to apoptotic stimuli has been unequivocally demonstrated. However, recent work has suggested that Bax/Bak may have unrecognized nonapoptotic functions related to mitochondrial function in nonstressful environments. Wild-type (WT) and Bax/Bak double knockout (DKO) mice were used to determine alternative...

Bax and Bak are known to play a central role in facilitating the release of mitochondrial intermembrane proteins during apoptosis. The detailed mechanism, however, is still not clear. Using live cell imaging techniques, we showed here that Bax underwent four distinct stages of dynamic redistribution during UV-induced apoptosis. At stage I, Bax was distributed diffusely in the cytosol. About an ...

Oncogenic transcription factor Myc deregulates the cell cycle and simultaneously reprograms cellular metabolism to meet the biosynthetic and bioenergetic needs of proliferation. Myc also sensitizes cells to mitochondria-dependent apoptosis. Although metabolic reprogramming has been circumstantially connected to vulnerability to apoptosis, the connecting molecular pathways have remained poorly d...

The proapoptotic members of the Bcl-2 family can be subdivided into members that contain several Bcl-2 homology (BH) domains and those that contain only the BH3 domain. Although it is known that BH3-only proteins and the multi-BH domain proteins, Bak and Bax, are essential for programmed cell death, the overlapping role of these two subgroups has not been examined in vivo. To investigate this, ...

Optical scatter imaging is used to estimate organelle size distributions in immortalized baby mouse kidney cells treated with 0.4 microM staurosporine to induce apoptosis. The study comprises apoptosis competent iBMK cells (W2) expressing the proapoptotic proteins Bax/Bak, apoptosis resistant Bax/Bak null cells (D3), and W2 and D3 cells expressing yellow fluorescent protein (YFP) or YFP fused t...

BAK activation represents a key step during apoptosis, but how it converts into a mitochondria-permeabilizing pore remains unclear. By further delineating the structural rearrangements involved, we reveal that BAK activation progresses through a series of independent steps: BH3-domain exposure, N-terminal change, oligomerization, and membrane insertion. Employing a "BCL-XL-addiction" model, we ...

The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 early-stage and 14 advanced-stage cancers). The data herein demonstrate, for the ...

Department of Horticultural Science (V.S.B., X.W., S.K.M., S.K., G.A., S.D.C.) and Department of Molecular and Structural Biochemistry (R.K.B., M.B.G.), North Carolina State University, Raleigh, North Carolina 27695; Plant and Crop Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom (E.L.W.); East Malling Research, East Malling, Kent ME19 6BJ, United Kingdom (G.J.B.); and Uni...