Iron deficiency accelerates intervertebral disc degeneration 2018

[pattismith]

2018

Iron deficiency accelerates intervertebral disc degeneration through affecting the stability of DNA polymerase epsilon complex (nih.gov)

Abstract

Iron serves as an important cofactor of iron-containing proteins that play critical roles in the maintenance of DNA stability and cell cycle progression.

.... In this study, we found a clear correlation between iron deficiency and intervertebral disc degeneration (IDD).

Through microarray experiments, we found that a large number of genes were differentially expressed in tissues with different degrees of degeneration.

Among them, an iron-containing gene, PolE, the catalytic subunit of DNA polymerase epsilon (Polε), and the other two Polε subunits, including PolE2 and PolE3, were markedly downregulated, while some proteins involved in apoptosis such as Caspase-3 and -8 were significantly upregulated.

By supplementation with an iron chelator deferoxamine (DFO) or knocking down either iron divalentmetal transporter 1 (DMT1) or transferrin receptor 1 (TfR1) in the nucleus pulposus (NP) cells, we found that the protein levels of PolE complex members were dramatically reduced, whereas the intrinsic apoptotic pathway was activated. Interestingly, overexpression of PolE in NP cells knocked down with either DMT1 or TfR could not reverse the stability of PolE complex and apoptosis status.

In summary, our study suggests that iron deficiency is an important factor in the aggravation of IDD.

Proper iron supplementation may be an effective strategy to alleviate the symptoms of patients with IDD.

 

[lenora]

Thanks for the info. I have several disc problems but iron's hard because I also have very high BP and I'm on heparin. These discs have been a problem for years....probably caused by other congenital problems I have, but I'm living with them. I don't like hearing that a lack of iron can make the problem worse.

I'll bring this up with neurologist (who also believes in natural remedies) at my next appt. Thanks. Yours, L.

 

[pattismith]

Thanks for the info. I have several disc problems but iron's hard because I also have very high BP and I'm on heparin. These discs have been a problem for years....probably caused by other congenital problems I have, but I'm living with them. I don't like hearing that a lack of iron can make the problem worse.

I'll bring this up with neurologist (who also believes in natural remedies) at my next appt. Thanks. Yours, L.

Lenora, both iron deficiency and iron overload can produce damages.
Having herniated discs doesn't mean you necessarily have iron deficiency!

It means that if you have associated herniated disc and iron deficiency, it might be important to adress the iron issue...

 

[Judee]

I do wonder if some pathogenic bacteria is using up our iron supplies and if that is why so many seem to have deficiencies in these chronic disease groups.

 

[pattismith]

I do wonder if some pathogenic bacteria is using up our iron supplies and if that is why so many seem to have deficiencies in these chronic disease groups.

your question already interested a scientist!

Some bacteria lower gut iron absorption when iron intake is low:

Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis

2019

Nupur K.Das1

https://doi.org/10.1016/j.cmet.2019.10.005


Highlights

•
Lactobacillus species sense intestinal iron levels and attenuate host iron absorption
•
Microbial metabolites DAP and reuterin are novel HIF-2α inhibitors
•
Gut microbial metabolites regulate intestinal iron storage via ferritin regulation
•
Gut microbiota can be therapeutically targeted for iron-related disorders

Summary

Iron is a central micronutrient needed by all living organisms.

Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial populations and for host health.

How symbiotic relationships between hosts and native microbes persist during times of iron limitation is unclear.

Here, we demonstrate that indigenous bacteria possess an iron-dependent mechanism that inhibits host iron transport and storage.

Using a high-throughput screen of microbial metabolites, we found that gut microbiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α) a master transcription factor of intestinal iron absorption and increase the iron-storage protein ferritin, resulting in decreased intestinal iron absorption by the host.

We identified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibition of heterodimerization.

DAP and reuterin effectively ameliorated systemic iron overload.

This work provides evidence of intestine-microbiota metabolic crosstalk that is essential for systemic iron homeostasis.