Proteomic identification of altered proteins in skeletal muscle during chronic potassium depletion: Implications for hypokalemic myopathy.
Prolonged potassium depletion is a well-known cause of myopathy. The pathophysiology of hypokalemic myopathy, however, remains unclear. We performed a gel-based, differential proteomics study to define altered proteins in skeletal muscles during chronic potassium depletion. BALB/c mice were fed with normal chow (0.36% K+) or K+-depleted (KD) diet (<0.001% K+) for 8 weeks (n = 5 in each group). Left gastrocnemius muscles were surgically removed from each animal. Histopathological examination showed mild-degree infiltration of polymornuclear and mononuclear cells at the interstitium of the KD muscles. Extracted proteins were resolved with two-dimensional electrophoresis (2-DE), and visualized with Coomassie Brilliant Blue R-250 stain. Quantitative intensity analysis revealed 16 up-regulated protein spots in the KD muscles, as compared to the controls. These differentially expressed proteins were subsequently identified by peptide mass fingerprinting and by quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Most of the altered proteins induced by chronic potassium depletion were muscle enzymes that play significant roles in several various metabolic pathways. Other up-regulated proteins included myosin-binding protein H, alpha-B Crystallin, and translationally controlled tumor protein (TCTP). These findings may lead to a new roadmap for research on hypokalemic myopathy, to better understanding of the pathophysiology of this medical disease, and to biomarker discovery.
Thongboonkerd
Visith
V
Medical Molecular Biology Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. thongboonkerd@dr.com
Kanlaya
Rattiyaporn
R
Sinchaikul
Supachok
S
Parichatikanond
Paisal
P
Chen
Shui-Tein
ST
Malasit
Prida
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D020514:Hypokalemic Periodic Paralysis / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D010449:Peptide Mapping; D011191:Potassium Deficiency / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D017422:Sequence Analysis, DNA; D000090324:Tumor Protein, Translationally-Controlled 1
D011506:Proteins; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1