Mitochondria-derived superoxide links to tourniquet-induced apoptosis in mouse skeletal muscle

Our previous study has reported that superoxide mediates ischemia-reperfusion (IR)-induced necrosis in mouse skeletal muscle. However, it remains poorly understood whether IR induces apoptosis and what factors are involved in IR-induced apoptosis in skeletal muscle. Using a murine model of tournique...

Full description

Saved in:
Bibliographic Details
Published inPloS one Vol. 7; no. 8; p. e43410
Main Authors Tran, Thai P, Tu, Huiyin, Liu, Jinxu, Muelleman, Robert L, Li, Yu-Long
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 17.08.2012
Public Library of Science (PLoS)
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Our previous study has reported that superoxide mediates ischemia-reperfusion (IR)-induced necrosis in mouse skeletal muscle. However, it remains poorly understood whether IR induces apoptosis and what factors are involved in IR-induced apoptosis in skeletal muscle. Using a murine model of tourniquet-induced hindlimb IR, we investigated the relationship between mitochondrial dysfunction and apoptosis in skeletal muscle. Hindlimbs of C57/BL6 mice were subjected to 3 h ischemia and 4 h reperfusion via placement and release of a rubber tourniquet at the greater trochanter. Compared to sham treatment, tourniquet-induced IR significantly elevated mitochondria-derived superoxide production, activated opening of mitochondrial permeability transition pore (mPTP), and caused apoptosis in the gastrocnemius muscles. Pretreatment with a superoxide dismutase mimetic (tempol, 50 mg/kg) or a mitochondrial antioxidant (co-enzyme Q(10), 50 mg/kg) not only decreased mitochondria-derived superoxide production, but also inhibited mPTP opening and apoptosis in the IR gastrocnemius muscles. Additionally, an inhibitor of mPTP (cyclosporine A, 50 mg/kg) also inhibited both mPTP opening and apoptosis in the IR gastrocnemius muscles. These results suggest that mitochondria-derived superoxide overproduction triggers the mPTP opening and subsequently causes apoptosis in tourniquet-induced hindlimb IR.
Bibliography:Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: TPT YLL. Performed the experiments: TPT HT JL YLL. Analyzed the data: TPT HT RLM YLL. Contributed reagents/materials/analysis tools: TPT HT JL YLL. Wrote the paper: TPT RLM YLL.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0043410