Unfolded Protein Response and A Possible Treatment for CFS

[Gondwanaland]

Hi,
Do you have any links where I can read more about molybdenum increasing bile flow? I can't find anything about this attribute of molybdenum.

Sorry, I don't. It is from personal observation. But I think it links with Sulfite Oxidase and endogenous generation of Taurine.

A word of caution about Molybdenum: it depletes Magnesium really quickly.

 

[Gondwanaland]

I am also under the impression that Moly, in addition to vit C, has a role in the conversion of Beta-Carotenes into vitamin A via Xanthine Oxidase.

I suppose this is why people who have gout/high uric acid issues are advised to eat lots of colorful vegetables rich in B-Carotenes and vit C. This mechanism will divert Moly from producing more uric acid.

 

[jason30]

Sorry, I don't. It is from personal observation. But I think it links with Sulfite Oxidase and endogenous generation of Taurine.

A word of caution about Molybdenum: it depletes Magnesium really quickly.

Thanks for the caution. I need moly for my MCS but on the other hand I always need extra magnesium.

 

[Gondwanaland]

Thanks for the caution. I need moly for my MCS but on the other hand I always need extra magnesium.

I am trying to up my intake of real vit A to improve oral tolerance. Very tricky.
https://www.selfhacked.com/blog/oral-tolerance/

 

[Violeta]

I am sure you already know this but I was so happy to find it that I just had to link it here.

Acetylcholine ameliorates endoplasmic reticulum stress in endothelial cells after hypoxia/reoxygenation via M3 AChR-AMPK signaling.
https://www.ncbi.nlm.nih.gov/pubmed/26066647

See if you find this interesting, too.
Endoplasmic reticulum stress contributes to acetylcholine receptor degradation by promoting endocytosis in skeletal muscle cells.
https://www.ncbi.nlm.nih.gov/pubmed/26711579

 

[Violeta]

I see @Gondwanaland beat me to the vitamin c link. But here's some additional info.
"Symptoms of vitamin C deficiency, such as poor wound healing and lethargy, result from impairment of these enzymatic reactions and insufficient collagen, carnitine, and catecholamine synthesis (see Deficiency). Research also suggests that vitamin C is involved in the metabolism of cholesterol to bile acids."

 

[sb4]

Acetylcholine ameliorates endoplasmic reticulum stress in endothelial cells after hypoxia/reoxygenation via M3 AChR-AMPK signaling.
https://www.ncbi.nlm.nih.gov/pubmed/26066647

This is very interesting. I wonder if you could help me understand it. I took a test last year that measured antibodies against adrenergic and muscarinic receptors. All mine where very low except for M3 which was just below the at risk range. So this one was significantly higher than the rest.

My main problem is heart pounding, followed by gastroparesis, POTS, dry mouth. It seems the M3 receptor is responsible for salivation, gut motility, and contracting blood vessels. As you can see these all relate directly to my main symptoms. I tried Bethanechol for an online pharmaciy (not sure of quality) and it made me worse for a few days.

The second study you linked seems to suggest that ER stress causes muscarinic receptors to degrade. Could it also cause increased antibodies to them?

The first study says that the pathway to healthy Hypoxia/Reoxygenation reaction is activating M3 receptors, which then activate AMPk. ER stress blocks M3, so could you get around this by doing other things to activate AMPk?

 

[Violeta]

This is very interesting. I wonder if you could help me understand it. I took a test last year that measured antibodies against adrenergic and muscarinic receptors. All mine where very low except for M3 which was just below the at risk range. So this one was significantly higher than the rest.

My main problem is heart pounding, followed by gastroparesis, POTS, dry mouth. It seems the M3 receptor is responsible for salivation, gut motility, and contracting blood vessels. As you can see these all relate directly to my main symptoms. I tried Bethanechol for an online pharmaciy (not sure of quality) and it made me worse for a few days.

The second study you linked seems to suggest that ER stress causes muscarinic receptors to degrade. Could it also cause increased antibodies to them?

The first study says that the pathway to healthy Hypoxia/Reoxygenation reaction is activating M3 receptors, which then activate AMPk. ER stress blocks M3, so could you get around this by doing other things to activate AMPk?

Good questions, but I don't know, sorry. But one question that comes to mind is what is different about M3 receptors that they might be the only ones with raised antibodies?

 

[jason30]

@Violeta

FYI, I suffer from impaired production of Dopamine and also impaired metabolism of it.

@mariovitali Sorry if I missed it, but which genes are responsible for the impaired production of Dopamine and impaired metabolism? And do you take other things besides mucuna for raising dopamine (I can't take mucuna because of liver problems) ?

 

[Violeta]

@mariovitali Sorry if I missed it, but which genes are responsible for the impaired production of Dopamine and impaired metabolism? And do you take other things besides mucuna for raising dopamine (I can't take mucuna because of liver problems) ?

I don't know anything about genes, but look at this information about tyrosine and let me know if anything clicks. I am too tired to think atm.

https://en.wikipedia.org/wiki/Tyrosine

This page has the gene for the enzyme that turns tyrosine into l-dopa.
https://en.wikipedia.org/wiki/Tyrosine_hydroxylase

Tyrosine for balancing acetylcholine/dopamine.
"In dopaminergic cells in the brain, tyrosine is converted to L-DOPA by the enzymetyrosine hydroxylase (TH). TH is the rate-limiting enzyme involved in the synthesis of the neurotransmitterdopamine. Dopamine can then be converted into other catecholamines, such as norepinephrine (noradrenaline) and epinephrine (adrenaline)."

 

[Violeta]

@mariovitali, I was trying to figure out something about hair loss related to Lyme and its coinfections and saw that NK cells can both cause or inhibit the autoimmune reaction, mostly tied into having EBV. I looked up NK cells and endoplasmic reticulum and found this.

https://www.ncbi.nlm.nih.gov/pubmed/25548215

 

[Violeta]

@mariovitali, I realize your endoplasmic reticulum theory reversed the issues caused by your taking a medicine, but have the supplements you take also seemed to stop hair loss?

 

[Violeta]

Some viruses take advantage of a host's activated cellular stress response and are able to increase replication when Hsps are high. Several viruses in fact stimulate a major increase in Hsps toward this end, such as human papillomavirus (Song et al. 2010), adenovirus (Glotzer et al. 2000; Madara et al. 2005), polyomaviruses, and dengue viruses (Reyes-Del Valle et al. 2005). Other viruses, however, suffer a reduction in replication when host Hsps are high, such as human immunodeficiency virus (HIV) and influenza A, where Hsp70 inhibits viral gene expression and replication."

So whether you want to increase hsp 70 or not would depend on which virus you have.

So this explains why some people respond to arginine supplementation one way and other people another way.

If you have more than one virus and they respond in the opposite manner, you are in trouble.


arginine as potential stimulators of HSPs 25, 60, 70 and 90

 

[aquariusgirl]

I notice you guys are taking choline about 700 mg... .well, i just started with it.. and I needed 30,000 mg to see an effect... and I read where some folks are talking about getting their brains back with PC IVs.... hmm so what is going on here?

 

[Violeta]

Someone in a different group that I belong to just brought up "cori cycle" in a thread where endoplasmic reticulum was being discussed, and I found this: " the formation of glucose, occurs in the lumen of the endoplasmic reticulum". The glucose is formed from lactate. If this cycle doesn't occur, lactic acid builds up in the muscles.

 

[Violeta]

Someone in a different group that I belong to just brought up "cori cycle" in a thread where endoplasmic reticulum was being discussed, and I found this: " the formation of glucose, occurs in the lumen of the endoplasmic reticulum". The glucose is formed from lactate. If this cycle doesn't occur, lactic acid builds up in the muscles.

ER stress modulates cellular metabolism
https://www.ncbi.nlm.nih.gov/pubmed/21241252

Also, ER stress can contribute to soft tissue calcification.

http://atvb.ahajournals.org/content/atvbaha/33/10/2345.full.pdf

 

[Violeta]

This is just for conversation. Does soft tissue calcification cause fibromyalgia?
http://naturalpainreliefforfibromyalgia.com/tag/calcification

If so, then ER stress could be the cause of fatigue due to inability to convert lactate to glucose, depriving muscles of energy source and at the same time causing fibromyalgia by causing soft tissue calcification.


https://www.sciencedirect.com/topics/neuroscience/endoplasmic-reticulum
The endoplasmic reticulum (ER) is a multifunctional organelle that is specialized for lipid synthesis, Ca2+ homeostasis, and protein synthesis

 

[Violeta]

This study has so many implications concerning ER stress that for now I will just link it and I will slowly pull out areas for discussion.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC333343/

 

[Violeta]

If ER stress disrupts conversion of lactate to glucose, is ER stress the cause of cancer?

https://academic.oup.com/carcin/article/38/2/119/2709442

Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect

 

[mariovitali]

All of these are quite interesting @Violeta, Thanks.

However, I believe that ER Stress is only one piece of the puzzle.