Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia
Authors: Sylvie Montessuit
Pierre-Alain Vitte
Agnes Bombrun
Stanley J Korsmeyer
Dennis J Church
Matthias K Schwarz
Tatiana K Rostovtseva
Claudio Hetz
Agnes Hiver
Bruno Antonsson
Jean-Claude Martinou
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ischemic injuries; stroke; myocardial infarction; apoptotic cell death; mitochondrion-mediated apoptosis pathway
Affiliations: Serono Pharmaceutical Research Institute, 14 chemin des Aulx, CH-1228 Plan-les-Ouates, Geneva, Switzerland.

Abstract:  Ischemic injuries are associated with several pathological conditions, including stroke and myocardial infarction. Several studies have indicated extensive apoptotic cell death in the infarcted area as well as in the penumbra region of the infarcted tissue. Studies with transgenic animals suggest that the mitochondrion-mediated apoptosis pathway is involved in ischemia-related cell death. This pathway is triggered by activation of pro-apoptotic Bcl-2 family members such as Bax. Here, we have identified and synthesized two low molecular weight compounds that block Bax channel activity. The Bax channel inhibitors prevented cytochrome c release from mitochondria, inhibited the decrease in the mitochondrial membrane potential, and protected cells against apoptosis. The Bax channel inhibitors did not affect the conformational activation of Bax or its translocation and insertion into the mitochondrial membrane in cells undergoing apoptosis. Furthermore, the compounds protected neurons in an animal model of global brain ischemia. The protective effect in the animal model correlated with decreased cytochrome c release in the infarcted area. This is the first demonstration that Bax channel activity is required in apoptosis. 

Retracted: No

PubPeer comments:
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 2005 was an *annus horribilis* for the 99 year old pharmaceutical company Serono. The punishment meted out for promoting Serostim for off-label uses in the US was a cool 704,000,000 greenbacks. https: en.wikipedia.org wiki Serono As night follows day, in 2006, the 100 year old pharmaceutical company Serona was duly snapped up by Merck. Wikipedia indicates that the vestiges have long since been migrated to Darmstadt in Germany, well away from the pricey Swiss metropolis of Geneva. u2019Uge cost-savings presumably resulted? In that light, getting all hot and bothered over a spot of undeclared splicing in some 2005 images of Serono ImmunoBlots (SIBs), as the original poster did, barely registers as impactful. Yet, for those of us who have a strange and old-fashioned attachment to the scientific literature, the quality of scientific papers is something that is difficult to overlook. Viewing the manuscript as submitted by the authors, which JBC has kindly made available online, it would appear that the original Illustrator figures are faithfully embedded in the pdf file. SIBs first make an appearance in Fig. 3A,B ![image] There is more to mark up in these figures. But only the nerdiest of figure sleuths should seek to understand the non-destructive editing process as applied to the Fig. 4G SIBs. If anyone manages successfully, do report back your experiencesu2026 , 
 In Fig. 5C, one of the microscopy fields is a composite assembled from four overlapped elements ![image] , 
 #3 Here is Fig 4G with blot panels separated into constituent parts (using Illustrator and the submitted PDF). I can t really fathom what they were trying to accomplish. The last 3 lanes of the  Stauro panel is overlain with separate data, which might be a concern. Otherwise there is repeated stacking of related images on top of each other, for unclear purposes; it s not obviously deceptive, just kind of silly. ![file] , 
 #5 I was so secretly hoping that you might take a peek at Fig. 4G, *Leucanella* :-) My guess is that these are non-destructive edits retained in the image editing software, which I assume to have been Adobe Illustrator. But I could be wrong. It could also be that they are simply a set of serially pasted in efforts to optimise the partial gel slices to the figure creatoru2019s satisfaction. Either way, the NT and Stauro right side blanched backgrounds have been changed to a more plausible grey to better match the left side. Of course the right side of Stauro is also a mish-mash of superposed slices, hiding another clear gel band. Does not compute. If you have a better idea about what has happened in 4G, please elaborate. Moving on, here are the five elements that make the two gel slices originally suggested back in 2014 by 001 as being spliced. And so they were! ![image] Of course in those dark days, JBC did not have a Data Integrity Manager. It does now. Readers may assume that, unless the junk mail filter has been over-trained, the DIM has been invited to this discussion. One more thing: From time to time, Pharma gets on its high horse and points out the sloppy practices of Academia which they themselves would never do. I would gladly take that punishment without so much as a murmur, were it not for indications such as these that Pharma are a bunch of hypocrites who arenu2019t apparently any better. , 
 #2 There I was preparing to do one of those bothersome routines to change colours of the graphs, make one partially transparent, stretch and superpose, to show all the world that the plots are the same while the axes are different. But - oh joy - a simple and much faster levels adjustment unexpectedly revealed that the rightmost plot was pasted in and stretched relative to the axes! Is this normal operating procedure for research by Pharma? ![image] , 
 This paper has a correction: https: www.jbc.org content 287 53 44108.short  We recently discovered a mistake in Fig. 5A. Because the images obtained for the two inhibitors were extremely similar, the same image was mistakenly used for both inhibitors when the figure was prepared. We are unable to retrieve the original images and provide a corrected figure. This error does not change the interpretation of the results presented in this figure or any of the conclusions of the paper. ,