Androgen Receptor Counteracts Doxorubicin-Induced Cardiotoxicity in Male Mice

http://mend.endojournals.org/cgi/content/full/24/7/1338

Doxorubicin, the anticancer drug is used for the treatment of several types of cancer. In many cases the clinical use of Dox is being held back because of its cardiotoxicity. Here the protective role of the AR pathway in the heart is being tested. This group is showing how activation of AR can counteract the damaging effect of Dox.

The nice thing about this is how we keep thinking of AR specifically in prostate cancer and as a drug target that we want to decrease its activation, and here we get an example of the positive role of AR and how targeting its activation in different types of tissues and different types of cancers can do good.

http://www.sciencemag.org/cgi/rapidpdf/science.1189123v1.pdf
http://www.sciencemag.org/cgi/rapidpdf/science.1189123.pdf

The two papers both identified mir-33 as a regulator of cholesterol homeostasis, particularly through its inhibitory effect on ABCA1. Like some other miRs, mir33 lies within the SREBP2 intron and is cotranscribed with SREBP2, thus the regulation of cholesterol level is coordinated. It will be interesting to address mir33 function that is independent of SREBP2, which can be attained, for example, under a condition that SREBP2 proteolysis is blocked but the transcription is still responsive to cholesterol level changes. Another mir (let-7c) potentially targets CCR7, and it is shown in the screen to be affected by cholesterol change in macrophages, whereas in my screen( LXR activated vs not) there is not much change.

A Simple Method for Gene Expression and Chromatin Profiling of Individual Cell Types within a Tissue

This method would require making a transgenic animal, but is a pretty cool method to isolate particular cell types within a tissue to look at gene expression or chromatin structure. I am sure some company will get on it and the mice will be available in a few years.

Also, it has a video that sums up the whole paper and actually shows they guy performing the experiment.

http://www.cell.com/developmental-cell/abstract/S1534-5807%2810%2900249-2

An interesting read...

This is quickly becoming less of the future and more of the present...

The Path to Personalized Medicine

Extranuclear Estrogen Receptors Mediate the Neuroprotective Effects of Estrogen in the Rat Hippocampus

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009851

This manuscript shows that estrogen conjugates, which cannot enter the nucleus based on size or charge and therefore activate extranuclear estrogen receptor (ER), are protective against cerebral ischemia (i.e. strokes) in rats. The ability of rats to recover learning and memory skills following stroke is improved in the presence of estrogen conjugates and measured using a Morris water maze test, for which I found a cool video on YouTube (gotta love the background music):

http://www.youtube.com/watch?v=LrCzSIbvSN4

The authors associate this observation with increased survival of CA1 hippocampal neurons through increased AKT, ERK, and CREB activation and BDNF production, as well as downregulation of active JNK (known to activate apoptotic pathways).

CDK5 Modulates the Transcriptional Activity of the Mineralocorticoid Receptor and Regulates Expression of BDNF

http://mend.endojournals.org/cgi/content/full/24/5/941#T1

Michael and this same group previously published a paper looking at the effect of cdk5 signaling on GR phosphorylation in neurons. Now they extend their study to MR and the effect of cdk5 on its transcriptional activity. In the process of identifying the phospho-sites induced by cdk5 on MR, they also show that cdk5 induces hGR phosphorylation by mass spec at S267 (one of the same BDNF induced phospho-sites that we identified in our lab).

This paper is not particularly innovative but they do "good" science to address the molecular affects of cdk5 on MR and GR with relevance to action in the nervous system.