Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal.
Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal.
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DOI：
10.1042/bj20090934
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发表时间：
2009-10-23
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影响因子：
--
通讯作者：
Darley-Usmar VM
中科院分区：
文献类型：
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作者：
Hill BG;Dranka BP;Zou L;Chatham JC;Darley-Usmar VM
线粒体在介导细胞对急性和慢性心功能障碍期间形成的氧化剂的反应方面发挥着关键作用。人们普遍认为，当细胞受到压力时，线粒体能够利用“储备能力”，该储备能力可用于满足维持器官功能、细胞修复或活性物质解毒的增加的能量需求。这一假说进一步暗示，这种假定的储备能力的损伤或耗尽最终导致过度的蛋白质损伤和细胞死亡。然而，它一直很难充分评估这一假设，因为我们的许多信息的反应的线粒体氧化应激来自研究分离的线粒体从他们的细胞环境。因此，本研究的目的是确定是否“生物能量储备能力”确实存在于完整的心肌细胞，以及它是否用于响应由病理相关的反应性脂质物质4-羟基壬烯醛（HNE）诱导的应激。我们发现，完整的新生大鼠心室肌细胞表现出大量的生物能量储备能力基础条件下，然而，在暴露于病理相关浓度的HNE，耗氧量增加，直到这种储备能力耗尽。HNE处理耗尽储备能力导致呼吸抑制伴随蛋白质修饰和细胞死亡。这些数据表明，氧化脂质可能有助于通过降低生物能量储备能力的心肌细胞损伤。此外，这些研究证明了测量生物能量储备能力用于评估或预测细胞对压力的反应的实用性。
Mitochondria play a critical role in mediating the cellular response to oxidants formed during acute and chronic cardiac dysfunction. It is widely assumed that, as cells are subject to stress, mitochondria are capable of drawing upon a “reserve capacity” which is available to serve the increased energy demands for maintenance of organ function, cellular repair, or detoxification of reactive species. This hypothesis further implies that impairment or depletion of this putative reserve capacity ultimately leads to excessive protein damage and cell death. However, it has been difficult to fully evaluate this hypothesis since much of our information about the response of the mitochondrion to oxidative stress derives from studies on mitochondria isolated from their cellular context. Therefore, the goal of this study was to determine whether “bioenergetic reserve capacity” does indeed exist in the intact myocyte and whether it is utilized in response to stress induced by the pathologically relevant reactive lipid species 4-hydroxynonenal (HNE). We found that intact rat neonatal ventricular myocytes exhibit a substantial bioenergetic reserve capacity under basal conditions; however, on exposure to pathologically relevant concentrations of HNE, oxygen consumption was increased until this reserve capacity was depleted. Exhaustion of the reserve capacity by HNE treatment resulted in inhibition of respiration concomitant with protein modification and cell death. These data suggest that oxidized lipids could contribute to myocyte injury by decreasing the bioenergetic reserve capacity. Furthermore, these studies demonstrate the utility of measuring the bioenergetic reserve capacity for assessing or predicting the response of cells to stress.