Reduction of Mitochondria and Up regulation of Pyruvate Dehydrogenase Kinase 4 of Skeletal Muscle in Patients w/Chronic Kidney Disease, 2019, Gu et al

[Andy]

Aim
Muscle weakness is commonly among chronic kidney disease (CKD) patients. Muscle mitochondrial dysfunction and decreased pyruvate dehydrogenase (PDH) activity occur in CKD animals but have not been confirmed in humans, and changes in pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP) expression have not been evaluated in CKD muscle. We presume that the reduction of muscle mitochondria and post‐translational modification of PDH may cause muscle weakness in CKD patients. Herein, we explored changes in mitochondrial morphology, PDH expression and activity, and PDK/PDP expression in CKD patient muscle.

Methods
Twenty patients with stage 4‐5 CKD (CKD group) and 24 volunteers (control group) were included. Clinical characteristics, biochemical information and handgrip strength (HGS) were determined. Skeletal muscle samples were collected from eight stage 5 CKD patients from CKD group. Other 8 non‐CKD surgical subjects' muscle samples were collected as control. PDH activity was determined using a PDH enzyme activity assay kit, and real‐time PCR and western blotting analyses were performed to measure gene expression and protein levels, respectively. Transmission electron microscopy was used to study mitochondria morphology.

Results
CKD patients had lower HGS than non‐CKD subjects, and HGS was correlated with gender, age, hemoglobin and albumin. Mitochondria were decreased in end‐stage renal disease (ESRD) patients muscle. Mfn‐1 expression and phospho‐Drp1(S637)/Drp1 ratio were inhibited in the ESRD group, implicating dysfunctional mitochondrial dynamics. Muscle PDH activity and phosphor‐PDH(S293) were decreased in ESRD patient muscle, while PDK4 protein level was up regulated

Conclusion
Decreased mitochondria and PDH deficiency caused by up regulation of PDK 4 contribute to muscle dysfunction, and could be responsible for muscle weakness in CKD patients.

Paywall, https://onlinelibrary.wiley.com/doi/abs/10.1111/nep.13606
Sci hub, https://sci-hub.se/10.1111/nep.13606

 

[janice]

Very interesting.
This type of info always gives me hope that soon "they" will get around to doing more objective, scientifically validated and helpful biomedical tests on ME/CFS patients to finally get to grips with the variety of biomedical issues we have.
Thanks for posting.
My hope muscles need reviving at the mo. This helps.

 

[mariovitali]

Spot on @Andy !


Here is more for Chronic Kidney Disease, note how the topics matched for ME/CFS also match CKD, as discussed below :

- Here is one idea. I used my collected pubmed data to try to identify which medical topics (out of a total of 592) mention all of the terms that we have seen in ME/CFS research (e.g cardiolipin, sepsis, MAIT cells,pyruvate, lactate, leptin, TRAIL, etc - list not inclusive). This is the output from the run :

find . -type f -exec grep -q thyroid {} \; -exec grep -q exosome {} \; -exec grep -q hypoxia {} \; -exec grep -q sepsis {} \; -exec grep -q MAIT {} \; -exec grep -q leptin {} \; -exec grep -q pyruvate {} \; -exec grep -q lactate {} \; -exec grep -q virus {} \; -exec grep -q "bile acid" {} \; -exec grep -q acetylation {} \; -exec grep -q TRAIL {} \; -exec grep -q "creatine kinase" {} \; -exec grep -q DAMPs {} \; -exec grep -q "beta oxidation" {} \; -exec grep -q lysine {} \; -exec grep -q tyrosine {} \; -exec grep -l cardiolipin {} \;

./albumin.csv
./cd36.csv
./ckd.csv
./er.csv
./fatty_acid.csv
./glutamate.csv
./glycolysis.csv
./glycoproteins.csv
./gut.csv
./hepatocytes.csv
./il_6.csv
./inflammatory_cytokines.csv
./leptin.csv
./liver_disease.csv
./liver_injury.csv
./macrophage.csv
./p53.csv
./proteasome.csv
./retinoic_acid.csv
./ros.csv
./sepsis.csv
./tnf_alpha.csv

https://www.s4me.info/threads/dr-ro...posium-march-2019-australia.9240/#post-162824

 

[janice]

Mariovitali.....wow.
Very very interesting.