Institute of Physiology, Czech Academy of Sciences, Videnska 1083, 14220 Prague 4 Czech Republic.
Can J Physiol Pharmacol. 2019 Sep;97(9):808-814. doi: 10.1139/cjpp-2019-0060. Epub 2019 Mar 20.
Age and sex play an essential role in the cardiac tolerance to ischemia-reperfusion injury: cardiac resistance significantly decreases during postnatal maturation and the female heart is more tolerant than the male myocardium. It is widely accepted that mitochondrial dysfunction, and particularly mitochondrial permeability transition pore (MPTP) opening, plays a major role in determining the extent of cardiac ischemia-reperfusion injury. We have observed that the MPTP sensitivity to the calcium load differs in mitochondria isolated from neonatal and adult myocardium, as well as from adult male and female hearts. Neonatal and female mitochondria are more resistant both in the extent and in the rate of mitochondrial swelling induced by high calcium concentration. Our data further suggest that age- and sex-dependent specificity of the MPTP is not the result of different amounts of ATP synthase and cyclophilin D: neonatal and adult hearts, similarly as the male and female hearts, contain comparable amounts of MPTP and its regulatory protein cyclophilin D. We can speculate that the lower sensitivity of MPTP to the calcium-induced swelling may be related to the higher ischemic tolerance of both neonatal and female myocardium.
心脏的抵抗力在出生后成熟过程中显著下降，女性心脏比男性心肌更耐受。人们普遍认为，线粒体功能障碍，特别是线粒体通透性转换孔（MPTP）的开放，在决定心脏缺血再灌注损伤的程度方面起着主要作用。我们观察到，从新生儿和成年心肌以及成年雄性和雌性心脏分离的线粒体对钙负荷的 MPTP 敏感性不同。在高钙离子浓度诱导的线粒体肿胀的程度和速率方面，新生和雌性线粒体的抵抗力更强。我们的数据进一步表明，MPTP 的年龄和性别依赖性特异性不是由于 ATP 合酶和亲环素 D 数量的不同所致：新生儿和成年心脏与雄性和雌性心脏一样，含有可比数量的 MPTP 和其调节蛋白亲环素 D。我们可以推测，MPTP 对钙诱导的肿胀的敏感性较低可能与新生儿和女性心肌的较高缺血耐受性有关。
