title: Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Jong Woong
authors.initials: JW
authors.lastname: Park
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Qi
authors.forename: Yongting
authors.initials: Y
authors.lastname: Cai
authors.forename: Igor
authors.initials: I
authors.lastname: Zelko
authors.forename: John Q
authors.initials: JQ
authors.lastname: Liu
authors.forename: Long-En
authors.initials: LE
authors.lastname: Chen
authors.forename: James R
authors.initials: JR
authors.lastname: Urbaniak
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Folz
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase