Laboratory of Environmental Physiology, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel.
Am J Physiol Regul Integr Comp Physiol. 2012 Oct 15;303(8):R870-81. doi: 10.1152/ajpregu.00155.2012. Epub 2012 Aug 15.
Long-term heat acclimation (LTHA; 30 days, 34°C) causes phenotypic adaptations that render protection against ischemic/reperfusion insult (I/R, 30 min global ischemia and 40 min reperfusion) via heat acclimation-mediated cross-tolerance (HACT) mechanisms. Short-term acclimation (STHA, 2 days, 34 °C), in contrast, is characterized by cellular perturbations, leading to increased susceptibility to insults. Here, we tested the hypothesis that enhanced mitochondrial respiratory function is part of the acclimatory repertoire and that the 30-day regimen is required for protection via HACT. We subjected isolated hearts and mitochondria from controls (C), STHA, or LTHA rats to I/R, hypoxia/reoxygenation, or Ca2+ overload insults. Mitochondrial function was assessed by measuring O2 consumption, membrane potential (ΔΨm), mitochondrial Ca2+ ([Ca2+]m), ATP production, respiratory chain complex activities, and molecular markers of mitochondrial biogenesis. Our results, combining physiological and biochemical parameters, confirmed that mitochondria from LTHA rats subjected to insults, in contrast to C, preserve respiratory functions (e.g., upon I/R, C mitochondria fueled by glutamate-malate, demonstrated decreases of 81%, 13%, 25%, and 50% in O2/P ratio, ATP production, ΔΨm, and complex I activity, respectively, whereas the corresponding LTHA parameters remained unchanged). STHA mitochondria maintained ΔΨm but did not preserve ATP production. LTHA [Ca2+]m was significantly higher than that of C and STHA and was not affected by the hypoxia/reoxygenation protocol compared with C. Enhanced mitochondrial biogenesis markers, switched-on during STHA coincidentally with enhanced membrane integrity (ΔΨm), were insufficient to confer intact respiratory function upon insult. LTHA was required for respiratory complex I adaptation and HACT. Stabilized higher basal [Ca2+]m and attenuated Ca2+ overload are likely connected to this adaptation.
长期热适应（LTHA；30 天，34°C）导致表型适应，通过热适应介导的交叉耐受（HACT）机制对缺血/再灌注损伤（I/R，30 分钟全局缺血和 40 分钟再灌注）产生保护作用。相比之下，短期适应（STHA，2 天，34°C）的特点是细胞扰动，导致对损伤的敏感性增加。在这里，我们测试了以下假设：增强的线粒体呼吸功能是适应机制的一部分，并且需要 30 天的方案通过 HACT 来提供保护。我们将来自对照（C）、STHA 或 LTHA 大鼠的分离心脏和线粒体暴露于 I/R、缺氧/复氧或 Ca2+过载损伤下。通过测量 O2 消耗、膜电位（ΔΨm）、线粒体 Ca2+（[Ca2+]m）、ATP 产生、呼吸链复合物活性以及线粒体生物发生的分子标志物来评估线粒体功能。我们的结果结合生理和生化参数，证实与 C 相比，LTHA 大鼠的线粒体在受到损伤后仍能维持呼吸功能（例如，在 I/R 下，用谷氨酸-苹果酸供能的 C 线粒体的 O2/P 比值、ATP 产生、ΔΨm 和复合物 I 活性分别下降 81%、13%、25%和 50%，而相应的 LTHA 参数保持不变）。STHA 线粒体保持了ΔΨm，但未能维持 ATP 产生。与 C 相比，LTHA 的 [Ca2+]m 显著更高，并且不受缺氧/复氧方案的影响。增强的线粒体生物发生标志物在 STHA 期间被开启，同时膜完整性（ΔΨm）增强，但不足以在受到损伤时赋予完整的呼吸功能。LTHA 是呼吸复合物 I 适应和 HACT 的必要条件。稳定的更高基础 [Ca2+]m 和减轻的 Ca2+过载可能与这种适应有关。
