Aggeli Ioanna-Katerina, Koustas Evaggelos, Gaitanaki Catherine, Beis Isidoros
Department of Animal and Human Physiology, School of Biology, University of Athens, Panepistimioupolis, Athens, Greece.
J Exp Zool A Ecol Genet Physiol. 2013 Jul;319(6):328-39. doi: 10.1002/jez.1797. Epub 2013 Apr 29.
Amphibians are known to better tolerate and endure adverse environmental conditions such as redox imbalances conferred by reactive oxygen species (ROS), compared to mammals. Interestingly, the exact adaptation strategies and signaling mechanisms mediating these effects have not been fully elucidated. Therefore, in the present study, we probed into the molecular response of the isolated perfused Rana ridibunda heart to curcumin, in the context of mitogen-activated protein kinases (MAPKs) phosphorylation patterns and apoptotic markers occurrence. In particular, this polyphenol was found to exert a pro-oxidant effect in our model and to significantly upregulate p38-MAPK and JNKs phosphorylation (thus activation). The early apoptosis observed, substantiated by poly(ADP-ribose) polymerase (PARP) cleavage, was established to be JNKs- and ROS-mediated, while no involvement of p38-MAPK was detected. Subsequently, the pro-oxidative activity of curcumin was confirmed to mimic H(2) O(2). Furthermore, NADPH oxidase as well as Na(+) /K(+) -ATPase were found to mediate JNKs phosphorylation as well as PARP proteolytic cleavage. Curcumin exerts pleiotropic actions, both beneficial and detrimental and is currently the subject of intense scientific research. Being a low-molecular-weight antioxidant, it is intriguing to investigate curcumin's role in redox homeostasis in the amphibian heart, under conditions that apparently favor its pro-oxidative properties. Comparative studies of its multifaceted role in different species may contribute to the clarification of the signaling mechanisms it triggers and the terminal physiological response it confers. Collectively, this is to our knowledge, the first time that the signal transduction pathways stimulated by curcumin have been assessed in a non-mammalian species.
与哺乳动物相比，两栖动物已知能更好地耐受和承受不利的环境条件，如活性氧（ROS）导致的氧化还原失衡。有趣的是，介导这些效应的确切适应策略和信号机制尚未完全阐明。因此，在本研究中，我们在丝裂原活化蛋白激酶（MAPKs）磷酸化模式和凋亡标志物出现的背景下，探究了分离灌注的食用蛙心脏对姜黄素的分子反应。特别是，在我们的模型中发现这种多酚具有促氧化作用，并能显著上调p38-MAPK和JNKs的磷酸化（从而激活）。通过聚（ADP-核糖）聚合酶（PARP）裂解证实观察到的早期凋亡是由JNKs和ROS介导的，而未检测到p38-MAPK的参与。随后，证实姜黄素的促氧化活性可模拟H(2) O(2)。此外，发现NADPH氧化酶以及Na(+) /K(+) -ATP酶介导JNKs磷酸化以及PARP蛋白水解裂解。姜黄素具有多效性作用，既有有益的一面，也有有害的一面，目前是深入科学研究的主题。作为一种低分子量抗氧化剂，在明显有利于其促氧化特性的条件下，研究姜黄素在两栖动物心脏氧化还原稳态中的作用很有趣。对其在不同物种中的多方面作用进行比较研究，可能有助于阐明其触发的信号机制及其赋予的终末生理反应。据我们所知，这是首次在非哺乳动物物种中评估姜黄素刺激的信号转导途径。
