Unfolded Protein Response and A Possible Treatment for CFS

[ppodhajski]

FMN decreased my need for antioxidants.

I am finding the same thing. I am now off selenium, soon Vitamin C.

I sometimes go days without any supplements but the first thing I always need is FMN. I think I will always need Biotin.

But yes, the stamina...I can do 25 pushups easy now. A year ago I could not do four.

 

[Ema]

SOD activity lowers ROS and that lowers coritsol, low SOD raises cortisol.

http://www.ncbi.nlm.nih.gov/pubmed/17279464

If you cannot cite your sources and make me do it I have to assume you can't do it. I cannot find one study that says cortosol raises SOD levels.

You know what they say about those who assume...might want to work on your googling. I found this one in less than 5 seconds.

http://www.ncbi.nlm.nih.gov/pubmed/8107531

 

[Ema]

Here's another.

http://www.ncbi.nlm.nih.gov/pubmed/20528575

 

[Ema]

And another.

http://www.ncbi.nlm.nih.gov/pubmed/20965252

 

[ppodhajski]

You know what they say about those who assume...might want to work on your googling. I found this one in less than 5 seconds.

http://www.ncbi.nlm.nih.gov/pubmed/8107531

This study points to CRH, not cortisol. CRH is not cortisol.

CRH it raises ROS levels, while cortisol LOWERS it:
http://www.ncbi.nlm.nih.gov/pubmed/9667222

Serum cortisol concentrations were markedly elevated over basal and remained elevated throughout the first 8 hours of the experiment, returning to baseline at 24 hours. This inhibition of ROS generation by HC (and other glucocorticoids) may have a role to play in mediating the antiinflammatory action of corticosteroids.

 

[Violeta]

You know what they say about those who assume...might want to work on your googling. I found this one in less than 5 seconds.

http://www.ncbi.nlm.nih.gov/pubmed/8107531

We are trying to learn together in this thread, and remarks like the way this one started don't seem to fit in.

 

[Ema]

We are trying to learn together in this thread, and remarks like the way this one started don't seem to fit in.

I reacted to the rudeness displayed. There are ways to ask for further information that are polite.

In terms of CRH, um, well, it increases cortisol. So if CRH is increased, cortisol levels increase as well. And again, it's dose dependent which was exactly my point to begin with. The abstract you posted uses pharmacological doses, not physiological.

ETA this probably needs to be it's own thread if you want to continue to debate cortisol and it's immunomodulatory effects in humans so as not to take this one any further off topic.

 

[ppodhajski]

I reacted to the rudeness displayed. There are ways to ask for further information that are polite.

In terms of CRH, um, well, it increases cortisol. So if CRH is increased, cortisol levels increase as well. And again, it's dose dependent which was exactly my point to begin with. The abstract you posted uses pharmacological doses, not physiological.

But CRH also increases SOD, so does cortisol LOWER SOD?

 

[Ema]

But CRH also increases SOD, so does cortisol LOWER SOD?

NO, IT DOES NOT (always).

Especially valuable for immune response is cortisol's stimulation of the superoxide dismutase,[16] since this copper enzyme is almost certainly used by the body to permit superoxides to poison bacteria.

Flohe L, Beckman R, Giertz H, Loschen G (1985). "Oxygen Centered Free Radicals as Mediators of Inflammation". In Sies H. Oxidative stress. London: Orlando. p. 405. ISBN0-12-642760-7

 

[ppodhajski]

NO, IT DOES NOT (always).

Flohe L, Beckman R, Giertz H, Loschen G (1985). "Oxygen Centered Free Radicals as Mediators of Inflammation". In Sies H. Oxidative stress. London: Orlando. p. 405. ISBN0-12-642760-7

That is from wikipedia and it is not a quote from the book, it is a paraphrase that might be wrong. I have been looking for research that shows it increases SOD activity and I have not found one. Have you read that book?

In fact., this book says the exact opposite:
https://books.google.com/books?id=I...tisol stimulates superoxide dismutase&f=false

It says it right there, copper enzymes are inhibited by cortisol.

 

[Ema]

That is from wikipedia and it is not a quote from the book, it is a paraphrase that might be wrong. I have been looking for research that shows it increases SOD activity and I have not found one. Have you read that book?

In fact., this book says the exact opposite:
https://books.google.com/books?id=IbQNcNQd4RcC&pg=PA139&lpg=PA139&dq=cortisol stimulates superoxide dismutase&source=bl&ots=ILiFQ4ENaF&sig=KnIdsN0FN8jNuFTOBGEjRLW-ln0&hl=en&sa=X&ved=0CEsQ6AEwB2oVChMIr5jRmqHPxwIVglKICh0l3g2F#v=onepage&q=cortisol stimulates superoxide dismutase&f=false

It says it right there, copper enzymes are inhibited by cortisol.

Inverse shutdown = stimulation. Ie cortisol stimulates SOD which allows for more superoxide to poison bacteria.

 

[Violeta]

It probably would be a good idea to try to find the same information through a different author as he uses the word "inversely" too frequently.

 

[ppodhajski]

Inverse shutdown = stimulation. Ie cortisol stimulates SOD which allows for more superoxide to poison bacteria.

You are reading that wrong. Read the first sentence of that paragraph where it says copper enzymes are inhibited 50% by cortisol. SOD is a copper enzyme. SOD is inhibited by cortisol.

What you don't realize you were saying would mean cortisol is always an immune stimulant, and we know that is not true. This is the end of my discussion on this matter. Sorry. I put enough evidence out there. People can make up their own minds.

 

[Ema]

You are reading that wrong. Read the first sentence of that paragraph where it says copper enzymes are inhibited 50% by cortisol. SOD is a copper enzyme. SOD is inhibited by cortisol.

What you don't realize you were saying would mean cortisol is always an immune stimulant, and we know that is not true. This is the end of my discussion on this matter. Sorry. I put enough evidence out there. People can make up their own minds.

We'll have to agree to disagree.

I stand 100% behind my original statement that cortisol can behave as both an immune stimulant or an immunosuppressive agent depending on the circumstances and dose and the rest of the extremely complex interactions of the immune system.

I agree the evidence speaks for itself and people with an open mind about the subject that haven't been brainwashed into "cortisol equals immune suppression" will clearly be able to see that the subject isn't black or white.

We've gotten well off track on just one mechanism for such action when surely there are many.

 

[Violeta]

That's really difficult to understand, but this sentence stood out to me:

Further investigation of the effects of flavins revealed that the inhibition was caused by an elevation of NADP+ in the incubations and that the incorporation of a NADPH generating system abolished the inhibition. Therefore, neither flavins nor Co-enzyme Q directly affected the 4-ene-steroid 5 alpha-reductase activity."

@mariovitali , you just have to make sure you are cycling the nadp to nadph. Here's how that happens.

The major source of NADPH in animals and other non-photosynthetic organisms is thepentose phosphate pathway.

However, there are several other lesser-known mechanisms of generating NADPH, all of which depend on the presence of mitochondria. The key enzymes in these processes are:NADP-linked malic enzyme, NADP-linked isocitrate dehydrogenase, NADP-linkedglutamate dehydrogenase and nicotinamide nucleotide transhydrogenase.[1] The isocitrate dehydrogenase mechanism appears to be the major source of NADPH in fat and possibly also liver cells.[2] Also, in mitochondria, NADH kinase produces NADPH and ADP, using NADH and ATP as substrate

 

[Violeta]

Cortisol is not an immune stimulant under any conditions. If you think otherwise please cite you r source.

This simple statement is I think the first time I read something that made me realize I need to rest to get better, even when I have energy.

 

[Violeta]

Impaired ER function caused by factors such as inhibition of posttranslational modifications, altered ER Ca2+, increased protein synthesis, viral infection, temperature shock and energy depletion can lead to accumulation of unfolded or misfolded proteins in the ER, initiating ER stress.

Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life, and it regulates or supports a variety of important cardiovascular, metabolic,immunologic, and homeostatic functions.

 

[Violeta]

We do need our share of glucocorticoids.

"GCs are part of the feedback mechanism in the immune system that turns immune activity (inflammation) down. They are therefore used in medicine to treat diseases caused by an overactive immune system, such as allergies, asthma, autoimmune diseases, and sepsis. "

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674691/

Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins
Indrajit Das, Chin Wen Png, [...], and Michael A. McGuckin

 

[Gondwanaland]

We do need our share of glucocorticoids.

Do you mean glucocorticoid drugs?
Sorry, but I know less than zilch about this subject.

 

[Violeta]

2

Do you mean glucocorticoid drugs?
Sorry, but I know less than zilch about this subject.

No, but I have to admit, that's about as much as I know. I think we have to keep our own going in the right amounts.
To be announced!
Hopefully someone else will come along with more knowledge, and maybe @mariovitali will run a search for us.