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Unfolded Protein Response and A Possible Treatment for CFS

Violeta

Violeta

Senior Member
Messages
2,969
I will just mention that beta alanine is a precursor to HmG CoA because mine is going to arrive in the mail today and maybe somebody knows something about it.
 
Violeta

Violeta

Senior Member
Messages
2,969
Does this mean anything important?


"The Membrane-Associated Transient Receptor Potential Vanilloid Channel Is the Central Heat Shock Receptor Controlling the Cellular Heat Shock Response in Epithelial Cells"
 
mariovitali

mariovitali

Senior Member
Messages
1,214
Violeta said:
Does this mean anything important?


"The Membrane-Associated Transient Receptor Potential Vanilloid Channel Is the Central Heat Shock Receptor Controlling the Cellular Heat Shock Response in Epithelial Cells"
Click to expand...


It appears to be since Heat Shock response is the mechanism behind proper protein folding (please also read my signature-it mentions Chaperones and HSP-70):


Heat shock response
The cellular response to heat shock includes the transcriptional up-regulation of genes encoding heat shock proteins (HSPs) as part of the cell's internal repair mechanism.[1] They are also called stress-proteins.[2] and respond to heat, cold and oxygen deprivation by activating several cascade pathways. HSPs are also present in cells under perfectly normal conditions.[2] Some HSPs, called chaperones, ensure that the cell’s proteins are in the right shape and in the right place at the right time.[1][2] For example, HSPs help new or misfolded proteins to fold into their correct three-dimensional conformations, which is essential for their function.[2] They also shuttle proteins from one compartment to another inside the cell, and target old or terminally misfolded proteins to proteases for degradation.[2] Heat shock proteins are also believed to play a role in the presentation of pieces of proteins (or peptides) on the cell surface to help the immune system recognize diseased cells.[3]
Click to expand...
 
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Gondwanaland

Gondwanaland

Senior Member
Messages
5,095
Violeta

Violeta

Senior Member
Messages
2,969
So according to this, one would want to use TRPV1 agonists?

" We found in various non-cancerous and cancerous mammalian epithelial cells that the TRPV1 agonists, capsaicin and resiniferatoxin (RTX), upregulated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70 and Hsp90 respectively, while the TRPV1 antagonists, capsazepine and AMG-9810, attenuated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70, Hsp90, respectively. "

I had been avoiding TRPV1 agonists???
 
mariovitali

mariovitali

Senior Member
Messages
1,214
Violeta said:
So according to this, one would want to use TRPV1 agonists?

" We found in various non-cancerous and cancerous mammalian epithelial cells that the TRPV1 agonists, capsaicin and resiniferatoxin (RTX), upregulated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70 and Hsp90 respectively, while the TRPV1 antagonists, capsazepine and AMG-9810, attenuated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70, Hsp90, respectively. "

I had been avoiding TRPV1 agonists???
Click to expand...


Honestly, i do not know. There might be a positive effect from inducing HSP-70 but i do not know what impact it this would have in other functions.

May i ask, How did you come up with TRPV1?
 
Violeta

Violeta

Senior Member
Messages
2,969
mariovitali said:
Honestly, i do not know. There might be a positive effect from inducing HSP-70 but i do not know what impact it this would have in other functions.

May i ask, How did you come up with TRPV1?
Click to expand...

I was reading about salicylate sensitivity since I believed that the sensitivity is brought on by a run in with a pathogen, and someone was talking about trpv1. I had been familiar with calcium channels and their importance with mast cell degranulation, which also is common in people with a pathogen. Plus, with all the neurological and neurotransmitter issues in people with a pathogen, I had been thinking first that there was a neurotransmitter defiency, then a neurotransmitter error or blockage, but now am thinking a large part of the problem is right at the calcium channel. Hence, soft tissue calcification. So I continue to look for transient receptor channel issues. But it's confusing which way to deal with it.

I had been thinking I should tend towards menthol type substances during the summer to keep from overheating, and had found that the trpm8 is antagonistic (??) to trpv1. http://www.ncbi.nlm.nih.gov/pubmed/25480783
 
mariovitali

mariovitali

Senior Member
Messages
1,214
@Violeta

I see. I will be looking at TRPV1, for now this is a first list of how frequently TRPV1 is found in PubMed entries. each Topic is denoted as <topic.csv>. See how the first two topics (after TRPV) are calcium_homeostasis and irritable_bowel (ngf = nerve growth factor,rxr = retinoid x receptor, ros=reactive oxygen species, pxr=pregnane x receptor, scfa=short chain fatty acids) :


trpv.csv : 80.93 %
calcium_homeostasis.csv : 0.98 %
irritable_bowel.csv : 0.45 %
ngf.csv : 0.39 %
mast_cell_activation.csv : 0.32 %
vitamin_d3.csv : 0.31 %
neuronal_nos.csv : 0.30 %
monosodium_glutamate.csv : 0.23 %
rxr.csv : 0.21 %
curcumin.csv : 0.17 %
endothelial_nos.csv : 0.13 %
glutamate.csv : 0.12 %
osmolytes.csv : 0.11 %
acetylcholine.csv : 0.11 %
ros.csv : 0.10 %
phospholipid_human.csv : 0.09 %
nlinkedglycosylation.csv : 0.09 %
beta-alanine.csv : 0.09 %
er_stress.csv : 0.09 %
serotonin_levels.csv : 0.09 %
butyrate.csv : 0.08 %
dopamine.csv : 0.08 %
pxr.csv : 0.08 %
scfa.csv : 0.07 %
peroxynitrite.csv : 0.07 %
excitotoxicity.csv : 0.07 %
inflammatory_response.csv : 0.06 %
cyp3a4.csv : 0.06 %
omega3.csv : 0.06 %
gaba_human.csv : 0.06 %
glycosylation.csv : 0.05 %
acetyl-coa.csv : 0.05 %
sirt1.csv : 0.05 %
mitochondrial_dysfunction.csv : 0.05 %
dopamine_levels.csv : 0.05 %
magnesium_deficiency.csv : 0.05 %
p450oxidoreductase.csv : 0.05 %
caspase_human.csv : 0.04 %
hpa_axis.csv : 0.04 %
tinnitus.csv : 0.04 %
oxidative_stress_protection.csv : 0.04 %
neurite_outgrowth.csv : 0.03 %
mastocytosis.csv : 0.03 %
pregnenolone.csv : 0.03 %
inducible_nos.csv : 0.03 %
dysautonomia.csv : 0.03 %
p5p.csv : 0.03 %
cyp1a1.csv : 0.03 %
nafld.csv : 0.03 %
rar.csv : 0.03 %
taurine.csv : 0.02 %
pbmc.csv : 0.02 %
limbic_system.csv : 0.02 %
lipoic_acid.csv : 0.02 %
3betahsd.csv : 0.02 %
sshl.csv : 0.02 %
zinc_supplementation.csv : 0.02 %
heat_shock_protein.csv : 0.02 %
nadph_human.csv : 0.02 %
mthfr.csv : 0.02 %
l-dopa.csv : 0.02 %
steatohepatitis.csv : 0.02 %
cyp2d6.csv : 0.02 %
dht.csv : 0.02 %
amyloid.csv : 0.02 %
urea_cycle.csv : 0.02 %
nadh_human.csv : 0.02 %
n-acetylglucosamine.csv : 0.02 %
probiotics.csv : 0.02 %
advanced_glycation_end.csv : 0.02 %
cfs.csv : 0.02 %
glycoproteins.csv : 0.01 %
insulin_resistance.csv : 0.01 %
histone_deacetylase.csv : 0.01 %
resveratrol.csv : 0.01 %
uric_acid.csv : 0.01 %
microbiome_humans.csv : 0.01 %
cholestasis.csv : 0.01 %
ckd.csv : 0.01 %
tau.csv : 0.01 %
selenium.csv : 0.01 %
social_anxiety.csv : 0.01 %
gluten.csv : 0.01 %
panic_disorder.csv : 0.01 %
sinusitis.csv : 0.01 %
oxalates.csv : 0.01 %
hydroxysteroid_dehydrogenase.csv : 0.01 %
human_proteinuria.csv : 0.01 %
l_carnitine.csv : 0.01 %
cortisol_levels.csv : 0.01 %
Click to expand...
 
Violeta

Violeta

Senior Member
Messages
2,969
Gondwanaland said:
Curcumin is also a phase I inhibitor.
Click to expand...
I didn't realize that about curcumin, very helpful if you have porphyria for sure. I wonder if it helps with pyroluria.

It sounds like a negative thing that it inhibits phase I detoxification, but this explains how it may be helpful.

"Some (stored toxins) may be converted from relatively harmless substances into potentially carcinogenic substances. Excessive amounts of toxic chemicals such as pesticides can disrupt the P-450 enzyme system by causing over activity or what is called 'induction' of this pathway. This will result in high levels of damaging free radicals being produced. The danger is if these reactive molecules are not further metabolised by Phase II conjugation, they may cause damage to proteins, RNA, and DNA within the cell."
 
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Gondwanaland

Gondwanaland

Senior Member
Messages
5,095
@Violeta I suppose this is how curcumin (and quercetin) helps with asthma, rhinitis, and allergies.
You just gave me a huge insight :bulb: I just re-read pages 7-8 of the document linked in my sig "The Liver" with a whole new understanding :jaw-drop::thumbsup:
 
Violeta

Violeta

Senior Member
Messages
2,969
Gondwanaland said:
@Violeta I suppose this is how curcumin (and quercetin) helps with asthma, rhinitis, and allergies.
You just gave me a huge insight :bulb: I just re-read pages 7-8 of the document linked in my sig "The Liver" with a whole new understanding :jaw-drop::thumbsup:
Click to expand...

I will have to read those pages, too!

And look what I just found about beta alanine.

Found it here:
http://www.life-enhancement.com/magazine/article/2050-beta-alanine-fights-fatigue


"Moreover, according to a 2005 study, beta- alanine has additional properties which may be of physiological significance.1 Biological stress increases levels of beta-alanine, which regulates excitotoxic responses and prevents neuronal cell death. From this knowledge, the researchers hypothesized that beta- alanine’s protective role might involve preservation of enzyme structure and function. They monitored heat-induced changes in lactate dehydrogenase (LDH)—an enzyme that catalyses the interconversion of pyruvate and lactate as well as the concomitant interconversion of NADH and NAD+—in the presence and absence of beta-alanine, and observed that beta-alanine suppressed heat-induced LDH inactivation, prevented LDH aggregation, and reactivated thermally denatured LDH. From these observations, they concluded that beta- alanine has chaperone-like activityand may play a cellular role in the preservation of enzyme function. Thus beta-alanine acts like an osmolyte, and may be able to help with proper protein folding.

Reference

  1. Mehta AD, Seidler NW. Beta-alanine suppresses heat inactivation of lactate dehydrogenase. J Enzyme Inhib Med Chem 2005 Apr;20(2):199-203."
I just started taking it yesterday mixed with taurine.
 
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Violeta

Violeta

Senior Member
Messages
2,969
Gondwanaland said:
How much? How are you tolerating it? I know it would cause me a massive oxalate dump.
Click to expand...

I started the taurine about 10 days ago, and was having some interesting digestive reactions that I figured were from it increasing bile flow. I can't remember how much I was taking, either 1/8th or 1/4 tsp in some water. Yesterday and today I took 1/4 tsp with the 1/4 tsp of beta alanine.

The only thing I can think of that might relieve the oxalate dump is either baking soda or borax.
 
Violeta

Violeta

Senior Member
Messages
2,969
@mariovitali What do you suppose all the uric acid has to do with this?

[uric_acid, n-acetylglucosamine]: 70 ==> [choline_deficiency]: 70 <conf (1)> lift (2.19) lev (0.15) conv (38.08)
[uric_acid, misfolded_proteins]: 67 ==> [choline_deficiency]: 67 <conf (1)> lift (2.19) lev (0.14) conv (36.45)
[uric_acid, dolichol]: 66 ==> [choline_deficiency]: 66 <conf (1)> lift (2.19) lev (0.14) conv (35.91)
[n-acetylglucosamine, l_carnitine]: 75 ==> [choline_deficiency]: 75 <conf (1)> lift (2.19) lev (0.16) conv (40.8)
[n-acetylglucosamine, selenium_deficiency]: 72 ==> [choline_deficiency]: 72 <conf (1)> lift (2.19) lev (0.15) conv (39.17)
[n-acetylglucosamine, pqq]: 67 ==> [choline_deficiency]: 67 <conf (1)> lift (2.19) lev (0.14) conv (36.45)
 
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