TLR2 deficiency attenuates skeletal muscle atrophy in mice.
Oxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice. Immobilization for 2 weeks increased the expression of cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle weight loss and a reduction in treadmill running times induced by immobilization were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization-associated increases in ubiquitinated protein levels were lower in the TLR2 KO mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and increased the levels of ubiquitinated proteins, although these levels were increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a potential target for preventing skeletal muscle atrophy.
Department of Orthopedic Surgery, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Dae-Sung
DS
Kim
Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Hye-Na
HN
Cha
Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Hye Jun
HJ
Jo
Department of Anatomy, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
In-Hwan
IH
Song
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Suk-Hwan
SH
Baek
Department of Orthopedic Surgery, Gumi CHA University Hospital, Gumi 730-728, South Korea.
Jin-Myoung
JM
Dan
Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Yong-Woon
YW
Kim
Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Jong-Yeon
JY
Kim
Department of Internal Medicine, Kyungpook National University, Daegu 700-721, South Korea.
In-Kyu
IK
Lee
Department of Orthopedic Surgery, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Jae-Sung
JS
Seo
Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea. Electronic address: sypark@med.yu.ac.kr.
So-Young
SY
Park
D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D007103:Immobilization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010766:Phosphorylation; D050050:Protein Carbonylation; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics; D054875:Ubiquitination
D004179:Cobra Cardiotoxin Proteins; D016207:Cytokines; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
Atrophy; Cardiotoxin; Immobilization; Oxidative stress; Skeletal muscle; TLR2