Cancer Initiation: Wingspans antigens connect nutritional and toxicological pathologies to the immune system

Tuesday, January 17, 2017

Wingspans antigens connect nutritional and toxicological pathologies to the immune system

Introduction

 In the previous post concerning selenium nutrition, we included a reference to wingspans antigens, and concluded that mis-regulation of these genes causued an auto-immune response. This finding is logical, based upon the evidence, but not medically proven. By medically proven, that means that a clinical study of a large sample of patients with an autoimmune pathology must be tested to see if in fact wingspan antigen RNA and proteins are being produced where they are not normally expected. ( Normal expectation is in cancer tissues and germ line and stem cell tissues.)
 It has only been relatively recently that scientists have been considering the link between nutrition and epigenetics [1] , and even in the case of this 2016 reference, they are discussing the issue in livestock, not humans. None the less, as a review of the process we will include a short clip here, in order to demonstrate the current level of understanding of the nutritional foundations of epigenetics.
modifications
Dietary induced epigenetic have been studied in a variety of food animal or livestock species (Table Table11). Nutrients such as folic acid and betaine have been shown to influence the function of enzymes that participate in the methylation process (Van den Veyver, 2002). Folic acid and betaine undergo a series of chemical reactions that result in the production of methionine (Anderson et al., 2012). Subsequently, methionine is converted to SAM, which donates methyl groups to DNMTs. The DNMTs then covalently attach the methyl groups to the five position of a cytosine base.
                                                                Murdoch( 2016) [1]

Single carbon metabolic pathways

 In the Murdock quote, we refer to the "methylation process" that is supported by such nutrients as folic acid and betaine. There are quite a few other nutrients as well, which include b12 and selenuim, as well as just about all of the components of a "prenatal vitamin". Since a "methyl group" is the simplest carbohydrate with 1 carbon, the research media is not often refers to this as single carbon metabolism. Although single carbon metabolism is very complex, we are going to refer to it as an item, as the literature has begun doing.
  We see from the quote that single carbon metabolism supports DNMTs, or DNA methyl transferases.  The are the enzymes that actually attach methyl groups to DNA, precisely at the "five
 position on the cytosine base". These cytosines are typically on the promoter of a gene and associasted with a guanine so they are commonly referred to CpG islands, where C and G are nucleotides and the p represents the phosphate between them. When a promoter has been methylated, a gene called MeCP2 binds to the promoter, and that gene is blocked from being expressed. As such, this is the "currency" of cellular differentiation.

Wingspans Antigens

 For quite some time now, researchers have been studying a group of proteins that are only found on germ line cells and cancer cells. The current literature contains no known purpose of these antigens. We state here that these always suppressed antigens are a signal to the immune system that a cell is failing to suppress blocked genes. Another way to say this is the job of the DNMT's or methyl transferases is not being completed, for whatever reason. The presumed reason is that the cell has lost control of its cell cycle, as in the case of cancer. The descriptive term in cancer is global hypomethylation. This means that in cancer cells, the cells differentiation is progressively lost as a result of DNMT failure, for whatever reason.

The Rattlesnake Hypothesis


 This model is extended to include the observation that telomerase must be expressed for a clone of cells to become "immortal". With only a few exceptions ( the ALT pathway ), telomerase is expressed in almost all malignancies. We have called the symmetric relationship between telomerase and winapans antigens the rattlesnake hypothesis.

Conclusion

 But what about the case where DNMTs are failing, not because of the loss of control of the cell cycle as in cancer,  but because nutritional support of the single carbon metabolism pathway is insufficient? We might think about the case where b12 or folate is deficient, or the case where heavy metals such as mercury or lead is disrupting the single carbon metabolism pathway. In this case we do commonly observe "auto-immune" pathologies. The remaining concept to be verified is that in fact wingspans antigens are being expressed as a result of failure to suppress them properly, and they are triggering the immune response.


References

[1]  Murdoch BM, Murdoch GK, Greenwood S, McKay S. Nutritional Influence on Epigenetic Marks and Effect on Livestock Production. Front Genet. 2016 Oct 24;7:182.  2016. [PubMed]

 



No comments:

Post a Comment