Gene expression profiling in human skeletal muscle during recovery from eccentric exercise.
We used cDNA microarrays to screen for differentially expressed genes during recovery from exercise-induced muscle damage in humans. Male subjects (n = 4) performed 300 maximal eccentric contractions, and skeletal muscle biopsy samples were analyzed at 3 h and 48 h after exercise. In total, 113 genes increased 3 h postexercise, and 34 decreased. At 48 h postexercise, 59 genes increased and 29 decreased. On the basis of these data, we chose 19 gene changes and conducted secondary analyses using real-time RT-PCR from muscle biopsy samples taken from 11 additional subjects who performed an identical bout of exercise. Real-time RT-PCR analyses confirmed that exercise-induced muscle damage led to a rapid (3 h) increase in sterol response element binding protein 2 (SREBP-2), followed by a delayed (48 h) increase in the SREBP-2 gene targets Acyl CoA:cholesterol acyltransferase (ACAT)-2 and insulin-induced gene 1 (insig-1). The expression of the IL-1 receptor, a known regulator of SREBP-2, was also elevated after exercise. Taken together, these expression changes suggest a transcriptional program for increasing cholesterol and lipid synthesis and/or modification. Additionally, damaging exercise induced the expression of protein kinase H11, capping protein Z alpha (capZalpha), and modulatory calcineurin-interacting protein 1 (MCIP1), as well as cardiac ankryin repeat protein 1 (CARP1), DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. In summary, using DNA microarrays and RT-PCR, we have identified novel genes that respond to skeletal muscle damage, which, given the known biological functions, are likely involved in recovery from and/or adaptation to damaging exercise.
Mahoney
D J
DJ
Department of Medical Sciences, McMaster University Medical Center, 1200 Main Street W., Hamilton, Ontario, Canada.
Safdar
A
A
Parise
G
G
Melov
S
S
Fu
Minghua
M
MacNeil
L
L
Kaczor
J
J
Payne
E T
ET
Tarnopolsky
M A
MA
D000328:Adult; D051017:Apoptosis Regulatory Proteins; D001706:Biopsy; D051347:CapZ Actin Capping Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D015444:Exercise / Q000502:physiology*; D020869:Gene Expression Profiling; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C477529:CCAR1 protein, human; D051347:CapZ Actin Capping Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121958:DNAJB2 protein, human; D050956:HSP40 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; C489427:MYC protein, human; D018832:Molecular Chaperones; D009124:Muscle Proteins; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; C108612:RCAN1 protein, human; D017472:Receptors, Interleukin-1; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2