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00005768-201005001-0002000005768_2010_42_6_liao_inflammatory_5miscellaneous< 16_0_1_0 >Medicine & Science in Sports & Exercise© 2010 American College of Sports MedicineVolume 42(5) Supplement 1May 2010pp 6-7Eccentric Contraction Induces Inflammatory and Proteolytic Responses in Rat Skeletal Muscle: 606: June 2 9:30 AM - 9:45 AM[A-15 Free Communication/Slide - Eccentric Contractions and Muscle Injury: JUNE 2, 2010 9:30 AM - 11:30 AM: ROOM: 345]Liao, Peng; Zhou, Jinping; Zhang, Yong; Ji, Li Li FACSM1Tianjin University of Sport, Tianjin, China. 2University of Wisconsin-Madison, Madison, WI.Email: ji@education.wisc.edu (No disclosure reported)Eccentric contraction (EC) is known to elicit inflammation and damage in skeletal muscle. Tumor necrosis factor (TNF) a plays an important role in this pathogenesis but its role in EC is unclear.PURPOSE: (1) To investigate the gene expression of TNFa in rat skeletal muscle during and after an acute bout of downhill exercise and the signaling pathways; (2) to examine whether EC activates muscle ubiquitin-proteolytic pathway resulting in necrosis and damage.METHODS: Female Sprague-Dawley rats (age 3 mo) were randomly divided into five groups (N=6): ran on the treadmill at 25 m/min, -10% grade for 1 or 2 h and were killed immediately; ran for 2 h and killed at 6 h or 24 h after exercise; or killed at rest as controls (R).RESULTS: TNFa mRNA level and protein content showed progressive increases in the deep portion of vastus lateralis (DVL) and gastrocnemius (GAS) muscles during and after EC. These changes were accompanied by a progressive decrease of mitochondrial aconitase activity (a marker of superoxide generation) and nuclear factor (NF) κB activation. After 2-h exercise, elevation of serum TNFa, endotoxin, creatine kinase and malondialdehyde levels was evident, which persisted through 24 h post exercise. At 24 h, there were marked increases in H2O2 concentration, myleoperoxidase activity and endotoxin level along with nuclear accumulation of p65 in both DVL and GAS. The mRNA level of ubiquitin-conjugating enzymes (E2)-14k was progressively upregulated during exercise and recovery in both muscles, whereas the expression of the toll-like receptor 4 (TLR4) in DVL was down-regulated. Histochemical analysis revealed intensified neutrophil infiltration, edema and fiber necrosis in both muscles after exercise.CONCLUSION: Prolonged muscle EC can induce TNFa expression through NFkB signaling activated by increased reactive oxygen species generation and endotoxin release. These inflammatory and pro-oxidative responses may activate proteolytic pathways resulting muscle necrosis and oxidative damage.Eccentric Contraction Induces Inflammatory and Proteolytic Responses in Rat Skeletal Muscle: 606: June 2 9:30 AM - 9:45 AMLiao, Peng; Zhou, Jinping; Zhang, Yong; Ji, Li Li FACSMA-15 Free Communication/Slide - Eccentric Contractions and Muscle Injury: JUNE 2, 2010 9:30 AM - 11:30 AM: ROOM: 345542