View Full Version : Histone deacetylase inhibitors induce mitochondrial elongation.


SB_UK
06-18-13, 03:56 PM
Incredible set of papers have come out over the last few months.

So obvious !!!

http://www.ncbi.nlm.nih.gov/pubmed/21928346
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Histone deacetylase inhibitors induce mitochondrial elongation.
histone deacetylation inhibitors are operating at the level of the mitochondria -<- our Gods.

That's the missing link.

http://www.nature.com/ncb/journal/v13/n5/abs/ncb2220.html
---2---
During autophagy mitochondria elongate, are spared from degradation and sustain cell viability

DcGonzo
06-18-13, 04:05 PM
This goes over my head, what does it mean?

SB_UK
06-18-13, 04:19 PM
Inflammation (see exogenous endotoxin theory relating to all animal products and processed food - carrying an LPS load which systemically inflames human beings living to the Western diet).

Treatment eg anti-TNFs - knocks down inflammation successfully - but but but - left without protection vs. intracellular pathogens.

eg tuberculosis mycobacterium reactivated with anti-TNF drugs.

Very deep connection between clearing intracellular pathogens and tidying up the cell - fail to clear intracellular pathogens / tidy up the cell and (respectively) - opened up to infectious disease and cancer.

Loss of autophagy/apoptosis - noting connection between TNFa (Tumour Necrosis factor) - in use of the relatively new anti-TNF class.

-*-

As simple as that - diet is driving inflammation, we're countering with drugs which effectively wipe out inflammation - but we need the power of inflammation (eg TNFa) in eg autophagy in cancer prevention.

Histone deacetylase inhibitors operate at the level of the mitochondrial genome - to drive autophagy - impressive things - they're cleaning us from the inside too ... ...

Natural histone deacetylase inhibitor = beta hydroxybutyrate (produced in an exercising, fasting, calorically restricted vegan ketogenic living).

http://www.jci.org/articles/view/57748
Mitochondrial Ca2+ and ROS take center stage to orchestrate TNF-α–mediated inflammatory responses This represents a tipping point in cell survival: low levels of ROS generated at complex III can activate adaptive signaling pathways, but higher levels of ROS result in the release of cytochrome [I]c and cell death.

-*-

Extremely important - mitochondrial / TNF alpha based mechanism for autophagy and apoptosis.
Pro-inflammatory capacity necessary.

Chronic systemic inflammation from [1] exogenous endotoxin and [2] centrally [psych. stress] leads to diseases which we're correcting by dampening the immune system
- dampen the immune system and open the door to infectious disease/cancer.

Shared 'protection' mechanism versus intracellular pathogen and cancer via autophagy/apoptosis.

SB_UK
06-18-13, 04:23 PM
Chronic systemic inflammation from [1] exogenous endotoxin and [2] centrally [psych. stress] ...


We need a world without [2] social hierarchy (money,ownership) and where [1] real (fresh food isn't tainted by gram negative (LPS,endotoxin laden) bacteria) food.

And all of our problems 'll go away.

meadd823
06-23-13, 04:04 AM
This goes over my head, what does it mean?

Yeah when I read the initial link there was a distinct smell of bacon as my brain fried :D Not really a vegan diet but I not a vegetable -okay but only when I am sleeping. :rolleyes:

It's going to take a few moment from me to re-call where the heck I put that decoder ring It's been a while sense I used any of this stuff other than to determine if it is science not science or topic not topic sort of stuff


It's biology at a cellar level chunks in a bit of chemistry but it's all natural chemistry = organic is a matter of opinion :p

meadd823
06-23-13, 04:53 AM
okay the first link is about Histone deacetylase inhibitors which are like anti-seizure medications being used to regulate cellar life cycles so to speak as a means of cancer treatments


Naturally proteins are going to be involved but I am missing the link between meat eating and inflammation other than meat is an animal protein and rapidly processed by the body as compared to plant proteins.

It seem that I am failing to comprehend how plant proteins which take longer to process are any less inflammatory= In autoimmune circles is the gluten free diets are being purposed as a contributing factor to the immune dysfunction

Where as I can certainly understand where cortizole levels {my spell checker refuse to recognize } associated with stress would contribute to over all inflammation I am not able to make the link to ingesting animal proteins themselves. Naturally it is always suspect is what the animals ate or were injected with before becoming dinner themselves - which does bring in your profit money issues but in a different fashion.


The second link seems to indicate that starvation under specific circumstance does decrease cellar death by equalizing the overall cellular cycle but it only stand to reason there is a limit other wise starvation wouldn't cause death

During starvation, cellular cyclic AMP levels increase and protein kinase A (PKA) is activated. PKA in turn phosphorylates the pro-fission dynamin-related protein 1 (DRP1), which is therefore retained in the cytoplasm, leading to unopposed mitochondrial fusion. Elongated mitochondria are spared from autophagic degradation, possess more cristae, increased levels of dimerization and activity of ATP synthase, and maintain ATP production.

Conversely, when elongation is genetically or pharmacologically blocked, mitochondria consume ATP, precipitating starvation-induced death. Thus, regulated changes in mitochondrial morphology determine the fate of the cell


Yeah I am missing some thing in the translation here = one forum of deprovasion is good the other not so good is about all I am getting out of that one but admittedly in the US it is early morning I may be suffering fro some sleep deprovasion myself I am trying to understand - I am surprized I am startng to recall some of this information it's been a while

Deceleration of Fusion–Fission Cycles Improves Mitochondrial Quality Control during Aging (http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002576)


Although our study clearly focuses on the role of mitochondrial dynamics in the ageing process it has the potential to challenge our current view on mitochondrial quality control in general. Changes in fusion–fission dynamics were recently observed under different physiological situations. After starvation or under certain stress conditions mitochondria were reported to undergo hyperfusion due to reduced DRP1-dependent mitochondrial fission [83]–[85]. Mitochondrial hyperfusion after starvation was not only shown for several cell lines but also for primary mouse hepatocytes [84]. Also progression from G1 to S phase requires hyperfusion of mitochondria whereas mitochondria fragment prior to cell division [40]–[42]. From these studies one can safely predict that fusion–fission rates are strongly dependent on the type of tissue (whether it is post-mitotic such as neurons or not) and on the metabolic state. Still, one needs to emphasize that there are hardly any quantitative data from primary tissues available. Based on this shortage of fundamental data, we feel that it is important to consider the possibility that mitochondrial content mixing by fusion–fission events can have beneficial as well as detrimental effects. The parameters when one or the other is dominating in vivo still need to be determined

SB_UK
06-23-13, 07:12 AM
...

Thanks - that's the connection -
back in a bit.

post-edit
described here:
http://www.addforums.com/forums/showpost.php?p=1502596&postcount=23

SB_UK
06-23-13, 07:26 AM
Publication stating the gaping hole that is mitochondrial histone modification.

It's where it's at!

Mitochondrial DNA: a blind spot in neuroepigenetics (http://www.degruyter.com/view/j/bmc.2012.3.issue-2/bmc-2011-0058/bmc-2011-0058.xml)

SB_UK
06-23-13, 07:29 AM
It seem that I am failing to comprehend how plant proteins which take longer to process are any less inflammatory

Back in a mo' to read the paper properly
... ... have to go clean a garage!!

Answer here - only 2 1/2 mins of your time.
http://www.youtube.com/watch?v=9Pnan0ETlVE

endotoxin/LPS --- SFA --- TLRs --- Inflammation

So now that we know what's going on - what do we do ?
To stop eating animal (SFA and gram neg containing bacteria) products

Endotoxin/LPS enriched in animal and processed products.
SFAs in animal products.

Note - chocolate (because of fermentation process and make-up) contains both gram negative and SFAs and causes inflammation
... ... so it's not just processed, animal products - it's anything with gram neg and SFA content.

-*-

This idea is totally attractive - because of a publication (presented by Michael Gregor) on the well characterized systemic inflammatory pattern post-eating (I'll find the video/paper later, if you like) ... ... which was part of the original rationale for the world decrying fat ... ... turns out that we'd missed the observation (lack in sensitivity of detection systems) - that it wasn't really the fat (SFA) in isolation -
it was simply allowing the most potent (LPS,endotoxin) activators of the immune system (so potent that they're the mechanism used in the lab to drive an immune reaction in vitro)
- a way into the human body.

Such a lovely, simple explanation underlying systemic inflammation (alongside the idea in the parallel thread of inflammator regulatory failure through cortisol resistance).

SB_UK
06-23-13, 08:00 AM
...

And finally ... ...

http://www.addforums.com/forums/showpost.php?p=1502607&postcount=25

"Exercise in the cold, whilst intermittently fasting and living a calorically restricted [FRESH VEGAN] ketotic lifestyle <- good stress."

-<- Optimal lifestyle,

as long as ->-

everything to do with money and social hierarchy <- toxic p$ych. and physical stress - which kill us are eradicated.

SB_UK
06-23-13, 08:14 AM
Currently working on the idea that the more mitochondria the better.
(I'm characterizing them as health protective).

So -
starvation -> mitoch. fusion -> reduced numbers -> bad (lower metabolism).
starvation state mimic (eating ketogenic diet) -> mitoch. fission -> increased numbers -> good (increased metabolism).

Working on the basis that ketogenic diet (which can be quite high) mimic of the state of starvation is optimal for the lil' guys.

Favours fission not fusion.

Reference I usually use:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867088/

"We propose an anticonvulsant mechanism of the KD involving mitochondrial biogenesis ... ..."

SB_UK
06-23-13, 08:19 AM
It seem that I am failing to comprehend how plant proteins which take longer to process are any less inflammatory= In autoimmune circles is the gluten free diets are being purposed as a contributing factor to the immune dysfunction


That's interesting - gluten's wiped out in a vegan ketogenic (too many carbs in wheat and friends) ... ... though (just checking):

seitan
fat - 2
carbs - 15
protein - 75

... ... would be the test.

-- gluten exorphin and caseomorphin - I think, though - may be 'out' for different reasons.

Also - I'm having an immune reaction to all seeds/nuts ... .. which appears to be eliminated by soaking/dehydration (this morning's expt)

- perfectly sensible - lectin elimination.

meadd823
06-26-13, 04:20 PM
I'm still with ya, you know it take me a while to read and digest {pun intended} I am also beginning to understand how you are connecting this diet to ADHD. I shall use the reference below so other members who might happen along can understand how the connection is being made and why

Neuroprotective and disease modifying effects of ketogenic diet (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/?report=reader)

Alternatively, the diet might protect against β-amyloid toxicity. Thus, direct application of β-hydroxybutyrate in concentrations produced by the ketogenic diet has been found to protect hippocampal neurons from toxicity induced by Aβ(1–42)

I believe most agree that the hippocampus, is highly suspect in ADD as well because as it has to do with converting short term memory to long term as well as memory retrieval and comparison

For any one who happens to be following along and is in need of a medical reference point for hippocampus (http://thebrain.mcgill.ca/flash/d/d_07/d_07_cr/d_07_cr_tra /d_07_cr_tra.html)

meadd823
06-26-13, 04:29 PM
I think the tipping point for me understanding wise is when stress goes from neuropriotective to neurodestructive - If this works much muscle masses in exercise some stress is good as long as the body has a recoup time where it can mend or recover - The protective is in the mending.


To be honest I have not caught up far enough to actually make that determination with regards to diet - For the gluten free diet glutens are not reintroduced at all except to remind folks why they were eliminated in the first place. :rolleyes:

I so miss chocolate cake and brownies!!!!! :(

There are obvious things about dietary changes that may be unique to that approach.



Must vacuum floor in living room before dust bunnies take over house. Later I shall look into the plant proteins verse animal proteins thing which is still my :scratch: