Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse

Jong Woong Park, Wen Ning Qi, Yongting Cai, Igor Zelko, John Q. Liu, Long En Chen, James R. Urbaniak, Rodney J. Folz

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)H181-H187
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number1 58-1
DOIs
Publication statusPublished - 2005 Jul

Keywords

  • Blood flow
  • Reactive oxygen species
  • Vessel diameter

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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