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2018 ; 19
(1
): 45
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Phosphate stimulates myotube atrophy through autophagy activation: evidence of
hyperphosphatemia contributing to skeletal muscle wasting in chronic kidney
disease
#MMPMID29486729
Zhang YY
; Yang M
; Bao JF
; Gu LJ
; Yu HL
; Yuan WJ
BMC Nephrol
2018[Feb]; 19
(1
): 45
PMID29486729
show ga
BACKGROUND: Accelerated muscle atrophy is associated with a three-fold increase
in mortality in chronic kidney disease (CKD) patients. It is suggested that
hyperphosphatemia might contribute to muscle wasting, but the underlying
mechanisms remain unclear. Although evidence indicates that autophagy is involved
in the maintenance of muscle homeostasis, it is not known if high phosphate
levels can result in activation of autophagy, leading to muscle protein loss.
METHODS: Immortalized rat L6 myotubes were exposed to a high concentration of
phosphate, with or without autophagy inhibition. Myotube atrophy was examined by
phase contrast microscopy. Autophagic activity was assessed by measuring the
expression of microtubule-associated protein 1 light chain 3 (LC3) and p62 using
quantitative real-time polymerase chain reaction and western blot. RESULTS:
Phosphate induced cell atrophy in L6 myotubes in a dose- and time-dependent
manner, and these responses were not associated with calcification or
osteogenesis. Phosphate also dose- and time-dependently increased the
LC3-II/LC3-I ratio. Inhibition of autophagy with wortmannin or knockdown of Atg5
significantly suppressed myotube atrophy caused by high phosphate concentration.
CONCLUSIONS: High phosphate concentration induces muscle cell atrophy through the
activation of autophagy. Targeting autophagy could be a therapeutic strategy for
preventing muscle wasting caused by hyperphosphatemia.