Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse.
This study investigates the role of extracellular SOD (EC-SOD), the major extracellular antioxidant enzyme, in skeletal muscle ischemia and reperfusion (I/R) injury. Pedicled cremaster muscle flaps from homozygous EC-SOD knockout (EC-SOD-/-) and wild-type (WT) mice were subjected to 4.5-h ischemia and 90-min reperfusion followed by functional and molecular analyses. Our results revealed that EC-SOD-/- mice showed significantly profound I/R injury compared with WT littermates. In particular, there was a delayed and incomplete recovery of arterial spasm and blood flow during reperfusion, and more severe acute inflammatory reaction and muscle damage were noted in EC-SOD-/- mice. After 90-min reperfusion, intracellular SOD [copper- and zinc-containing SOD (CuZn-SOD) and manganese-containing (Mn-SOD)] mRNA levels decreased similarly in both groups. EC-SOD mRNA levels increased in WT mice, whereas EC-SOD mRNA was undetectable, as expected, in EC-SOD-/- mice. In both groups of animals, CuZn-SOD protein levels decreased and Mn-SOD protein levels remained unchanged. EC-SOD protein levels decreased in WT mice. Histological analysis showed diffuse edema and inflammation around muscle fibers, which was more pronounced in EC-SOD-/- mice. In conclusion, our data suggest that EC-SOD plays an important role in the protection from skeletal muscle I/R injury caused by excessive generation of reactive oxygen species.
Park
Jong Woong
JW
Department of Orthopaedic Surgery, College of Medicine, Korea University, Seoul, Korea.
Qi
Wen-Ning
WN
Cai
Yongting
Y
Zelko
Igor
I
Liu
John Q
JQ
Chen
Long-En
LE
Urbaniak
James R
JR
Folz
Rodney J
RJ
D000818:Animals; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply*; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase