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

Thai P. Tran, Huiyin Tu, Jinxu Liu, Robert Leo Muelleman, Yulong Li

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 Q10, 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.

Original languageEnglish (US)
Article numbere43410
JournalPloS one
Volume7
Issue number8
DOIs
StatePublished - Aug 17 2012

Fingerprint

tourniquets
Tourniquets
Mitochondria
ischemia
Superoxides
superoxide anion
Reperfusion
Muscle
skeletal muscle
Skeletal Muscle
mitochondria
Ischemia
apoptosis
Apoptosis
mice
permeability
Hindlimb
coenzyme Q10
muscles
Rubber

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Mitochondria-derived superoxide links to tourniquet-induced apoptosis in mouse skeletal muscle. / Tran, Thai P.; Tu, Huiyin; Liu, Jinxu; Muelleman, Robert Leo; Li, Yulong.

In: PloS one, Vol. 7, No. 8, e43410, 17.08.2012.

Research output: Contribution to journalArticle

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