Schisandrin B decreases the sensitivity of mitochondria to calcium ion-induced permeability transition and protects against ischemia-reperfusion injury in rat hearts.
OBJECTIVE
In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions.


RESULTS
Myocardial I-R injury caused an increase in the sensitivity of mitochondria to Ca2+-stimulated PT in vitro. The enhanced sensitivity to mitochondrial PT was associated with increases in mitochondrial Ca2+ content as well as the extent of reactive oxidant species production in vitro and cytochrome c release in vivo. The cardioprotection afforded by Sch B pretreatment against I-R-induced injury was paralleled by the decrease in the sensitivity of myocardial mitochondria to Ca2+-stimulated PT, particularly under I-R conditions.


CONCLUSIONS
The results suggest that Sch B treatment increases the resistance of myocardial mitochondria to Ca2+-stimulated PT and protects against I-R-induced tissue injury.
Chiu
Po-Yee
PY
Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong SAR, China.
Leung
Hoi-Yan
HY
Siu
Ada Hl
AH
Poon
Michel Kt
MK
Ko
Kam-Ming
KM
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000302:isolation & purification / Q000494:pharmacology; D034242:Cyclooctanes / Q000302:isolation & purification / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D010946:Plants, Medicinal / Q000737:chemistry; D011083:Polycyclic Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry
D002316:Cardiotonic Agents; D034242:Cyclooctanes; D017705:Lignans; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C015499:schizandrin B; D045304:Cytochromes c; D002118:Calcium