CoQ10 enhances PGC1α and increases expression of mitochondrial antioxidant proteins in chronically ischemic swine myocardium

被引:9
作者
Hocum Stone, Laura [1 ,2 ]
Chappuis, Erin [1 ]
Wright, Christin [1 ,2 ]
Kelly, Rosemary F. [1 ,2 ]
McFalls, Edward O. [3 ,4 ]
机构
[1] Univ Minnesota Twin Cities, Dept Surg, Minneapolis, MN USA
[2] Minneapolis VA Med Ctr, Res Serv, Minneapolis, MN USA
[3] Univ Minnesota Twin Cities, Dept Med, Minneapolis, MN 55455 USA
[4] Minneapolis VA Med Ctr, Cardiol 111C, 1 Vet Dr, Minneapolis, MN 55417 USA
关键词
Hibernating myocardium; CoQ(10); Mitochondria; PGC1; alpha; TRANSPORT CHAIN PROTEINS; CORONARY-ARTERY-DISEASE; HIBERNATING MYOCARDIUM; MAGNETIC-RESONANCE; COENZYME Q(10); HEART-FAILURE; DOUBLE-BLIND; STRESS; AUTOPHAGY; PROTECTS;
D O I
10.1186/s12986-019-0418-8
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Background Expression of mitochondrial proteins is reduced within hibernating myocardium (HM). It is unclear whether dietary supplementation with CoQ(10) can increase expression of mitochondrial electron transport chain (ETC) and antioxidant proteins within this tissue. In a swine model of HM, we tested whether dietary administration of CoQ(10) for four weeks enhances the expression of ETC and antioxidant proteins within the mitochondria via increased PGC1 alpha signaling. Methods 12 swine were instrumented with a fixed constrictor around the LAD artery to induce gradual stenosis. At three months, transthoracic ECHO was performed to confirm the presence of a wall motion abnormality in the anterior wall. Animals were then randomly assigned to receive daily dietary supplements of either CoQ(10) (10 mg/kg/day) or placebo for four weeks. At this time, animals underwent a final ECHO and terminal procedure. Expression of nuclear-bound PGC1 alpha (Western blots) and mitochondrial proteins (Tandem Mass Tag) were determined. Results Mitochondrial and nuclear membranes were isolated from the LAD region. Nuclear-bound PGC1 alpha levels were > 200-fold higher with administration of four weeks of CoQ(10) treatment (p = 0.016). Expression of ETC proteins was increased in those animals that received CoQ(10). Compared with mitochondria in the LAD region from placebo-treated pigs, CoQ(10)-treated pigs had higher levels of Complex I (p = 0.03), Complex IV (p = 0.04) and Complex V (p = 0.028) peptides. Conclusions Four weeks of dietary CoQ(10) in HM pigs enhances active, nuclear-bound PGC1 alpha and increases the expression of ETC proteins within mitochondria of HM tissue.
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页数:10
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