Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning
Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning
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DOI：
10.1152/ajpheart.00372.2011
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发表时间：
2012-05-01
影响因子：
4.8
通讯作者：
McFalls, Edward O.
中科院分区：
文献类型：
--
作者：
Cabrera, Jesus A.;Ziemba, Elizabeth A.;McFalls, Edward O.
卡布雷拉JA，Ziemba EA，Colbert R，Anderson LB，Sluiter W，Duncker DJ，Butterick TA，Sikora J，Ward HB，Kelly RF，McFalls EO。晚期缺血预适应期间线粒体电子传输链蛋白表达的改变和心肌能量状态的改善。Am J Physiol心圈Physiol 302：H1974-H1982,2012。2012年3月2日首次出版；doi：10.1152/ajpheart.00372.2011。-在早期预适应的心肌组织中显示出线粒体电子传输蛋白的表达改变。我们希望确定这些改变是否持续在第二保护窗(SWOP)，如果是的话，是否在随后的缺血期间促进了良好的能量状态。14只猪接受了SWOP方案，在LAD动脉内进行10次2分钟的球囊充气，每次间隔2分钟再灌流。24小时后，从SWOP和假手术猪心脏中分离线粒体，用Western印迹分析解偶联蛋白(UCP)-2的含量，用iTRAQ(R)分析蛋白质组的变化，用氧电极分析呼吸作用。在平行的活体研究中，通过对麻醉的SWOP和假手术猪在基线和持续低流量缺血期间进行跨壁活组织检查，获得高能核苷酸。与假手术组相比，体外培养的SWOP心肌组织中UCP-2、复合体IV(细胞色素c氧化酶)和复合体V(ATPase)蛋白表达增加。在活体条件下，与假手术猪相比，SWOP心脏的跨壁能量能(用ATP水解自由能(Delta G(0))估计)在基线时相似，但在低流量缺血结束时降低(-57.0+/-2.1比-51.1+/-1.4kJ/mol；P<；0.05)。总之，在预适应的SWOP心脏的分离线粒体中，UCP-2增加，并与增强的复合体IV和V蛋白协同作用，在低流量缺血时给予良好的能量状态。这些数据支持这样一种观点，即在持续缺氧期间，线粒体的适应可能会减少氧化剂损伤，但不会降低能量的整体效率。
Cabrera JA, Ziemba EA, Colbert R, Anderson LB, Sluiter W, Duncker DJ, Butterick TA, Sikora J, Ward HB, Kelly RF, McFalls EO. Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning. Am J Physiol Heart Circ Physiol 302: H1974-H1982, 2012. First published March 2, 2012; doi: 10.1152/ajpheart.00372.2011.-Altered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated during subsequent ischemia. Fourteen pigs underwent a SWOP protocol with ten 2-minute balloon inflations in the LAD artery, each separated by 2 minutes reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP and SHAM pig hearts and analyzed for uncoupling protein (UCP)-2 content by western blot analysis, proteomic changes by iTRAQ (R) and respiration by an oxygen electrode. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during sustained low-flow ischemia. Compared with SHAM mitochondria, ex vivo SWOP heart tissue demonstrated increased expression of UCP-2, Complex IV (cytochrome c oxidase) and Complex V (ATPase) proteins. In comparison with SHAM pigs during in vivo conditions, transmural energetics in SWOP hearts, as estimated by the free energy of ATP hydrolysis (Delta G(0)), were similar at baseline but had decreased by the end of low-flow ischemia (-57.0 +/- 2.1 versus -51.1 +/- 1.4 kJ/mol; P < 0.05). In conclusion, within isolated mitochondria from preconditioned SWOP hearts, UCP-2 is increased and in concert with enhanced Complex IV and V proteins, imparts a favorable energetic state during low-flow ischemia. These data support the notion that mitochondrial adaptations that may reduce oxidant damage do not reduce the overall efficiency of energetics during sustained oxygen deprivation.