My response to #NUB6S3/CI3 overgrew a reasonable comment size, so it would be a post.
Рассмотрим highlights «той самой статьи» (http://www.cell.com/neuron/abstract/S0896-6273(14)00196-2)
1. HSF1 is activated in the cortex by various types of prenatal environmental stresses.
HSF1 exists as an inactive monomer in a complex with Hsp40/Hsp70 and Hsp90. Upon stress, such as elevated temperature, HSF1 is released from the chaperone complex and trimerizes. HSF1 is then transported into the nucleus where it is hyperphosphorylated and binds to DNA containing heat shock elements (NGAAN). HSF1's target genes include major inducible heat shock proteins such as Hsp72, and interestingly, noncoding RNA within Satellite III repeat regions. Its attenuation phase is initiated as a negative feedback loop with its gene product Hsp70 binding to its transactivation domain. [Shamovsky I, Nudler E (March 2008). "New insights into the mechanism of heat shock response activation". Cell. Mol. Life Sci. 65 (6): 855–861]
Здесь еще проще и понятнее написано:
The heat shock transcription factor (HSF) is a trimer that binds to DNA containing inverted repeats of the sequence nGAAn. HSF can bind DNA with the sequence nGAAnnTTCn or with the sequence nTTCnnGAAn, with little preference for either sequence over the other. [http://www.ncbi.nlm.nih.gov/pubmed/8264619]
И что же означает оседание белка на ДНК?
In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator. A DNA-binding repressor blocks the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes into messenger RNA. [http://en.wikipedia.org/wiki/Repressor]
But is HSF1 a repressor for some essential gene? Hell, yes!
HSF1 represses the lipopolyliposaccharide-induced transcription of theIL-1β promoter through direct interaction with the nuclear factor of interleukin 6 (NF-IL6, also known asCCAAT enhancerbindingprotein (C/EBPβ), an essential regulator inIL-1β transcription. We show for the first time that HSF1 binds directly to NF-IL6 in vivo and antagonizes its activity. [http://www.jbc.org/content/277/14/11802.full.pdf]
Let’s read a bit about IL1B function.
IL-1 proteins are considered endogenous pyrogens since they are involved in inflammatory responses and also have been observed to foment prostaglandin and collagenase release from synovial cells. Additionally, IL-1 is responsible for the induction of IL-2 release, B-cell maturation/proliferation, and fibroblast growth factor activity, that stimulates thymocyte proliferation. [http://atlasgeneticsoncology.org/Genes/GC_IL1B.html]
Wow, a lot of medical terminology. Let’s google “Low IL1B”.
Low concentration of interleukin-1beta induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets. [http://www.ncbi.nlm.nih.gov/pubmed/17003335]
Sounds scary.
The primary function of a beta cell is to store and release insulin. Insulin is a hormone that brings about effects which reduce blood glucose concentration. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting some of their stored insulin while simultaneously producing more.
Sounds like diabetes.
type 2 is characterized by both high glucose levels, and high insulin levels in the blood. The main problem is that the body's tissues are resistant to insulin, and can't use it properly
Drawing up the results, we illustrated how high HSF1 may cause a malfunction in human body system. Wait a sec – HSF1 is high in the cortex, but beta cells are in pancreas! That’s a thing to think about. I’m not enthusiastic enough to do it in the short term.
Btw, HSF1 has been shown to interact with lots of proteins (http://en.wikipedia.org/wiki/HSF1).
@ceyt спрашивает, как происходящее связано с памятью. Интересно, как выключение какого-то гена в клетках кортекса повлияет на память? Да, при чем тут память вообще, кортекс какой-то, гены какие-то выключаются!
Furthermore, compared with wild-type littermates, mice lacking NMDA receptors in the primary motor cortex show slower learning in Skinner-box tasks. Thus, primary motor cortex NMDA receptors are necessary for activity-dependent synaptic strengthening and associative learning. http://www.ncbi.nlm.nih.gov/pubmed/23978820
Glutamate [NMDA] receptor subunit epsilon-2 also known as N-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B) is a protein that in humans is encoded by the GRIN2B gene.
GRIN2B has been shown to interact with some other genes too. (http://en.wikipedia.org/wiki/GRIN2B)
I am not going to dig into this gene mayhem for now, because I have a lot of work to do, but doesn’t it sounds as a plausible idea that if you invade cortex with a suppressor of one of the genes, a delicate balance of protein synthesis?
2. Loss of HSF1 increases seizure susceptibility upon prenatal exposure to challenges
It seems to explain why this malicious HSF1 is not as malicious as I depicted hereinbefore.
But I already have spent a significant amount of time on this post, so o lape pona.
