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

Autor: John Q. Liu, Rodney J. Folz, Yongting Cai, James R. Urbaniak, Wen Ning Qi, Long En Chen, Jong Woong Park, Igor N. Zelko
Rok vydání: 2005
Předmět:
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 289:H181-H187
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.00458.2004
Popis: 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.
Databáze: OpenAIRE