Human skeletal muscle biochemical diversity.
The molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain, MHC) and mechanosensitive signaling (titin) have been well studied in animals but less is known about their roles in humans. The purpose of this study was to perform a comprehensive analysis of titin, collagen and MHC isoform distributions in a large number of human muscles, to search for common themes and trends in the muscular organization of the human body. In this study, 599 biopsies were obtained from six human cadaveric donors (mean age 83 years). Three assays were performed on each biopsy - titin molecular mass determination, hydroxyproline content (a surrogate for collagen content) and MHC isoform distribution. Titin molecular mass was increased in more distal muscles of the upper and lower limbs. This trend was also observed for collagen. Percentage MHC-1 data followed a pattern similar to collagen in muscles of the upper extremity but this trend was reversed in the lower extremity. Titin molecular mass was the best predictor of anatomical region and muscle functional group. On average, human muscles had more slow myosin than other mammals. Also, larger titins were generally associated with faster muscles. These trends suggest that distal muscles should have higher passive tension than proximal ones, and that titin size variability may potentially act to 'tune' the protein's mechanotransduction capability.
Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA 92093, USA.
Timothy F
TF
Tirrell
Mark S
MS
Cook
J Austin
JA
Carr
Evie
E
Lin
Samuel R
SR
Ward
Richard L
RL
Lieber
D000368:Aged; D000369:Aged, 80 and over; D001669:Biochemical Phenomena; D003094:Collagen / Q000378:metabolism; D064211:Connectin; D016002:Discriminant Analysis; D005260:Female; D006112:Gravitation; D006801:Humans; D007596:Joints / Q000033:anatomy & histology; D008297:Male; D008970:Molecular Weight; D009124:Muscle Proteins / Q000737:chemistry; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology; D018995:Myosin Heavy Chains / Q000378:metabolism; D011494:Protein Kinases / Q000737:chemistry; D014019:Tissue Donors
D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D003094:Collagen; D011494:Protein Kinases; D018995:Myosin Heavy Chains