Muscari C, Biagetti L, Stefanelli C, Giordano E, Guarnieri C, Caldarera C M
Department of Biochemistry, University of Bologna, Italy.
J Mol Cell Cardiol. 1995 Jan;27(1):283-9. doi: 10.1016/s0022-2828(08)80027-2.
This study investigated the biosynthesis of ubiquinone in isolated and perfused hearts of young and aged rats exposed to ischemia and reperfusion. A first group of hearts was used to determine the changes in coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentrations at mitochondrial and microsomal level after 30 min of ischemia (98% reduction of the preischemic flow) and 60 min of reperfusion. A second group was utilized to evaluate the rate of CoQ9 and CoQ10 biosynthesis in the membranes by dissolving two ubiquinone precursors, p-OH-[U-14C]benzoate and mevalonolactone, in the perfusion buffer. The hearts were aerobically perfused for 60 min in the presence of the precursors either immediately after the equilibration period or following 30 min ischemia. The young rat hearts showed a 30% reduction in the mitochondrial levels of CoQ9 after ischemia and reperfusion with respect to the preischemic values (P < 0.05 and P < 0.01, respectively). On the contrary, the mitochondrial CoQ9 content was not modified under these conditions in the aged hearts. At the end of reperfusion, the biosynthesis of mitochondrial CoQ9 and CoQ10 was higher in the young rats (P < 0.05), and lower in the aged rats (P < 0.05), with respect to the aerobic perfusion. In both young and aged rats minor changes in CoQ9 concentrations and biosynthesis were observed at microsomal level. These results indicate that myocardial reperfusion decreases the mitochondrial content of ubiquinone and stimulates CoQ9 biosynthesis in young rats but not in aged rats.
本研究调查了年轻和老年大鼠离体灌注心脏在缺血再灌注情况下泛醌的生物合成。第一组心脏用于测定在缺血30分钟(缺血前血流量减少98%)和再灌注60分钟后线粒体和微粒体水平辅酶Q9(CoQ9)和辅酶Q10(CoQ10)浓度的变化。第二组用于通过将两种泛醌前体对羟基-[U-14C]苯甲酸酯和甲羟戊酸内酯溶解在灌注缓冲液中来评估膜中CoQ9和CoQ10的生物合成速率。在平衡期后立即或在缺血30分钟后,在有前体存在的情况下对心脏进行60分钟的有氧灌注。年轻大鼠心脏缺血再灌注后线粒体中CoQ9水平相对于缺血前值降低了30%(分别为P < 0.05和P < 0.01)。相反,在这些条件下老年心脏的线粒体CoQ9含量未发生改变。再灌注结束时,与有氧灌注相比,年轻大鼠线粒体CoQ9和CoQ10的生物合成较高(P < 0.05),老年大鼠较低(P < 0.05)。在年轻和老年大鼠的微粒体水平均观察到CoQ9浓度和生物合成的微小变化。这些结果表明,心肌再灌注会降低泛醌的线粒体含量,并刺激年轻大鼠而非老年大鼠的CoQ9生物合成。