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Effect of thyroid hormone T3 on mitochondrial properties in cells from patients with mtDNA defects

Discussion in 'Other Health News and Research' started by pattismith, Jan 30, 2018.

  1. pattismith

    pattismith Senior Member

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    Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects
    2009

    Abstract
    Mitochondrial (mt)DNA mutations contribute to various disease states characterized by low ATP production. In contrast, thyroid hormone [3,3′,5-triiodothyronine (T3)] induces mitochondrial biogenesis and enhances ATP generation within cells. To evaluate the role of T3-mediated mitochondrial biogenesis in patients with mtDNA mutations, three fibroblast cell lines with mtDNA mutations were evaluated, including two patients with Leigh's syndrome and one with hypertrophic cardiomyopathy. Compared with control cells, patient fibroblasts displayed similar levels of mitochondrial mass, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), mitochondrial transcription factor A (Tfam), and uncoupling protein 2 (UCP2) protein expression. However, patient cells exhibited a 1.6-fold elevation in ROS production, a 1.7-fold elevation in cytoplasmic Ca2+ levels, a 1.2-fold elevation in mitochondrial membrane potential, and 30% less complex V activity compared with control cells. Patient cells also displayed 20–25% reductions in both cytochrome c oxidase (COX) activity and MnSOD protein levels compared with control cells. After T3 treatment of patient cells, ROS production was decreased by 40%, cytoplasmic Ca2+ was reduced by 20%, COX activity was increased by 1.3-fold, and ATP levels were elevated by 1.6-fold, despite the absence of a change in mitochondrial mass. There were no significant alterations in the protein expression of PGC-1α, Tfam, or UCP2 in either T3-treated patient or control cells. However, T3 restored the mitochondrial membrane potential, complex V activity, and levels of MnSOD to normal values in patient cells and elevated MnSOD levels by 21% in control cells.
    These results suggest that T3 acts to reduce cellular oxidative stress, which may help attenuate ROS-mediated damage, along with improving mitochondrial function and energy status in cells with mtDNA defects.

    @BeautifulDay
     
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  2. Learner1

    Learner1 Professional Patient

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    Iinteresting! They seem to be able to measure the performance of mitochondria in research studies. Is there a way of measuring our membrane potential, free radical production and Complex I-V?
     
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  3. pattismith

    pattismith Senior Member

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    it's an In Vitro study, so I suppose it is easier to measure lot's of parameters.

    Full article is available if your brain is better than mine :):

    https://pdfs.semanticscholar.org/518a/ea6f524a5fabdb3921b009e3a89a947fdce0.pdf
     
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  4. BeautifulDay

    BeautifulDay Senior Member

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    @pattismith thank you for tagging me. Very interesting. A we'll known physician who specializes in thyroid issues sat next to me for a day at the last UMDF conference for physicians. He was telling me at break that he thought I should see a thyroid specialist and that the thyroid might be an avenue for adding in a treatment that might reduce the severity of some of my symptoms.

    The final paragraph of the paper:
    "In conclusion, the results of the present study indicate that fibroblast cells from patients with mtDNA defects exhibit lower COX activities despite having similar mitochondrial masses as control cells. Furthermore, these cells have higher levels of ROS and intracellular calcium, along with lower complex V activity. T3 treatment reversed these abnormalities by improving mitochondrial function and cellular energy status. Therefore, it may be suggested that potent and specific T3 analogs may be useful to reverse the pathophysiology of cells from patients with mtDNA defects and impaired organelle function."
     
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  5. pattismith

    pattismith Senior Member

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    It's amazing!
    I wonder if any mito specialist would give a try to use T3 to treat mito diseases or dysfunctions...
     
  6. aquariusgirl

    aquariusgirl Senior Member

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    @BeautifulDay

    Hi can you PM me or share the name of the thyroid specialist? Pretty sure I have a T3 problem. Thanks,
     
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  7. BeautifulDay

    BeautifulDay Senior Member

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    Somewhere in our house I have my papers and notes from that conference. No time today to search. I'm like many with chronic fatigue - never enough energy to put stuff away. I end up with piles and piles. Energy is spent on the days emergency or child needing something or hot issue. I'll look tomorrow. I need an emoji for my pile of laundry. It should have a big monster face.
     
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  8. mermaid

    mermaid Senior Member

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    I don't understand all the science of this, but wish I did as I took T3 only for 5 years and I can at least get the gist of this positive study. It took me a long while to improve significantly but several years in, my energy levels were much better. I had previously been on T4 only for 17 years during which time I acquired my CFS/ME status.

    I would still be on the T3 only if it hadn't been for the medical 'powers that be' insisting that I reduced it to 20mcg due to the osteoporosis diagnosis which they blamed on the T3. Since their 'treatment' over several months has significantly deteriorated my quality of life (less stamina, croaky voice, constant viruses), I have now been forced to reject their advice, and go my own way again, although at the moment I am retaining 25mcg T4 but doubt that much T4 gets converted from my blood into my cells.
     
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  9. aquariusgirl

    aquariusgirl Senior Member

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    @BeautifulDay ...do you remember the name of the researcher .... I could email & ask him for the doctor's name.
     
  10. sb4

    sb4 Senior Member

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    "In an experiment, rats were given a standard diet, to which had been added 1% Armour thyroid, that is, they were made extremely hyperthyroid. Since their diet was inadequate (later experiments showed that this amount of thyroid didn't cause growth retardation when liver was added to the diet) for their high metabolic rate, they died prematurely, in an apparently undernourished state, weighing much less than normal rats. Their bones, however, were larger and heavier than the bones of normal rats. A few incompetent medical "studies" have made people fear that "taking thyroid can cause osteoporosis." Recognizing that hypothyroid women are likely to have small bones and excessive cortisol production, the inadequate treatment of hypothyroidism with thyroxin (the thyroid-suppressive precursor material), is likely to be associated with relative osteoporosis, simply because it doesn't correct hypothyroidism. Similar misinterpretations have led people to see an association between "thyroid use" (generally thyroxin) and breast cancer--hypothyroid women are likely to have cancer, osteoporosis, obesity, etc., and are also likely to have been inadequately treated for hypothyroidism. T3, the active form of thyroid hormone, does contribute to bone formation. (For example, M. Alini, et al.)"
    http://raypeat.com/articles/articles/osteoporosis.shtml

    I know that it is current medical conventional wisdom that T3 = osteoporosis but it certainly isn't the only opinion and conventional wisdom currently is wrong on many many things IMO. Having said that I'm relatively new to learning about the thyroid but will try T3 soon.
     
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  11. bertiedog

    bertiedog Senior Member

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    I had to have a DEXA scan in 2012 because I have to take Prednisolone 6mg for adrenal insufficiency. However I have always taken 2 grains dessicated thyroid along with 25 mcg thyroxine along with the Pred since 2003. I have also been using just one squirt of Estrogel along with the above and also good supplements.

    To the amazement of my doctors and also the radiographer the scan showed I had the bones of a 30 year old despite the fact I was 64 at the time!

    In 2004 even though I had ME/CFS I did start to lift the lightest weights about 3 times a week for my upper body and continue to do this and I also manage to walk quite briskly every day for a minimum of 20 minutes but obviously when I am crashing or unwell with a virus I cannot do this so all in all I am very pleased that I stuck to what I had read from thyroid experts like Dr John Lowe and also I was very fortunate in that I came across a qualified private doctor who was a qualified Endo and first introduced me to my need for thyroid and adrenal support.

    If I had stuck with NHS treatment, I dread to think what I state I would be in by now as I approach my 70th birthday next month. They messed me up 18 months ago when I made the mistake of having a check up with an NHS Endo who insisted I was on too much thyroid medication for my BMI. He made me stop the thyroxine but it was a disaster and I lost many of the gains I had made. Luckily it was reflected in my blood tests so he had to agree I did need it but it all goes to show that just a tiny adjustment with regard to the thyroid (and adrenals) can make a massive difference to our quality of life especially when suffering with an illness like ME/CFS.


    Pam
     
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