Online Journal Club for January 2010
Welcome to the New Year. If you have articles that you believe should be included in the online journal club, send them to me before the 20th of the month.
*1. Global Shifts in Protein Sumoylation in Response to Electrophile and Oxidative Stress. Manza L et al, Chem Res Toxicol 2004(17)1706-1715.
Directly on point! These guys, from my alma mater of the University of Arizona, and from Vanderbilt, hit HEK293 cells with ROS and observed a global phase shift in the population of SUMOylated proteins. Proteomic analysis was done by mass spec, of course, but the actually retrieval of SUMOylated proteins was done by HA-tags, and so their methods are quite different from what we would need to do in the rat. Still, the population of SUMOylated proteins they retrieved under oxidative stress situations was intriguing, to say the least. Of course, they saw changes in the SUMOylation of transcriptional regulators, RNA processors, and the like, but they also saw changes in chaperone proteins, electron transport proteins, metabolic enzymes, VDAC, PCD5, ubiquitin conjugating enzyme E2L3, transketolase, 14-3-3 protein and--get this—cytochrome c.
From our work these last few months and from looking at the literature, I am getting the idea that we were naďve to think we could pull off a rat SUMO brain ischemia proteome in the time frame we envisaged. But it’s important to keep in mind that we originally dreamed up that project because we hadn’t seen a SUMO proteome in conditions relevant to ours. These gusy have done the work. There’s a ton of hypotheses sitting in this paper, just waiting for us to explore. Must read.
Link (PDF): http://pubs.acs.org/doi/pdf/10.1021/tx049767l?cookieSet=1
*2. Does the radial arm maze necessarily test spatial memory? Dubreuil D et al. Neurobiol Learn Mem 79 (2003) 109-117.
Part of our ongoing RAM project. The whole rationale for
this paper is the methodology, introduced early on, of confining the animals
very briefly within the arm they have just visited, in order to ablate innate
foraging strategies which may interfere with the ability to test working
memory. This is a long and occasionally difficult paper, but good for looking
at our evolving methodology. The take-home—for us—is neatly summarized at the
end: “To conclude, it seems that similar
levels of performances in a full-baited RAM can mask very different
representations. As mentioned by Olton (1987), the RAM is a tool to probe what
types of representations have been formed as a result of a given experience.
Thus, it is crucial that the experimenter clearly identifies what she or he
wants to study before choosingone or the other version of the full-baited maze
task. If the goal is to quantify the spontaneous strategies that are used to
perform the task, the non-confinement conditions are useful (Pico & Davis,
1984). However, if the goal is to study spatial memory per se, it is necessary
to use the confinement procedure. This is the reason why, a few years after the
original description of this task (Olton & Samuelson, 1976), the initial
protocol was modified to introduce a 15-s confinement between each arm visit
(Olton et al., 1977; Olton & Collison, 1979). This crucial step toward
studyingspati al memory using the radial arm maze should not be forgotten.”
*3. Translation of remote ischemic preconditioning into clinical practice. Kharbana RK et l. Lancet 2009 (374): 1557-65.
This paper, and the one that follow it, provide a nice chronicle of the remote ischemic pre/post-conditioning story. As you know, our own Dr. Przyklenk has been seminally involved in this process. Although some data suggests an autonomic component, the bulk of the evidence points toward a circulating factor.
*4. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Botker et al, Lancet 2010 (375): 727-34.
Alas, the story doesn’t end as neatly as we would like. I
usually don’t include clinical studies on the lab’s journal club, but in this
case it’s worth a read. After conducting a randomised trial of patients with
induced arm ischemia vs. no ischemia, who then underwent PTCA for heart attack,
the authors remport that remote ischemic conditioning increased myocardial
salvage and has a favourable safety profile. True, so far as it goes. But look
closer: preconditioning reduced total infarct size by a whopping 1% (p=.10).
The salvage index was 73 in patients with preconditioning and 69 in those without.
This was statistically significant, but its clinical significance is doubtful
at best. The final infarct size as a % of LV was different by only 4% (p=.62).
Finally, when the rubber met the road in patient-oriented outcomes, there was
nothing—the same number of patients in each group suffered reinfarction, heart
failure, and death. The joys of translational medicine.