Characterization of the human skeletal muscle proteome by one-dimensional gel electrophoresis and HPLC-ESI-MS/MS.
Changes in protein abundance in skeletal muscle are central to a large number of metabolic and other disorders, including, and perhaps most commonly, insulin resistance. Proteomics analysis of human muscle is an important approach for gaining insight into the biochemical basis for normal and pathophysiological conditions. However, to date, the number of proteins identified by this approach has been limited, with 107 different proteins being the maximum reported so far. Using a combination of one-dimensional gel electrophoresis and high performance liquid chromatography electrospray ionization tandem mass spectrometry, we identified 954 different proteins in human vastus lateralis muscle obtained from three healthy, nonobese subjects. In addition to a large number of isoforms of contractile proteins, we detected all proteins involved in the major pathways of glucose and lipid metabolism in skeletal muscle. Mitochondrial proteins accounted for 22% of all proteins identified, including 55 subunits of the respiratory complexes I-V. Moreover, a number of enzymes involved in endocrine and metabolic signaling pathways as well as calcium homeostasis were identified. These results provide the most comprehensive characterization of the human skeletal muscle proteome to date. These data hold promise for future global assessment of quantitative changes in the muscle proteome of patients affected by disorders involving skeletal muscle.
Højlund
Kurt
K
Center for Metabolic Biology, Arizona State University, Tempe, Arizona, USA.
Yi
Zhengping
Z
Hwang
Hyonson
H
Bowen
Benjamin
B
Lefort
Natalie
N
Flynn
Charles R
CR
Langlais
Paul
P
Weintraub
Susan T
ST
Mandarino
Lawrence J
LJ
D000328:Adult; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003285:Contractile Proteins / Q000032:analysis; D004579:Electron Transport; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I; D050356:Lipid Metabolism; D008875:Middle Aged; D008970:Molecular Weight; D009124:Muscle Proteins / Q000032:analysis* / Q000737:chemistry; D018482:Muscle, Skeletal / Q000737:chemistry*; D010085:Oxidative Phosphorylation; D021381:Protein Transport; D020543:Proteome / Q000032:analysis* / Q000737:chemistry; D040901:Proteomics; D021241:Spectrometry, Mass, Electrospray Ionization; D013347:Subcellular Fractions
D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D007328:Insulin; D009124:Muscle Proteins; D020543:Proteome; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D002118:Calcium