Lee Phil Jun, Cho Namki, Yoo Hee Min, Kim Hong Pyo
College of Pharmacy, Ajou University, Suwon, South Korea.
Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon, South Korea.
Front Physiol. 2020 Jan 15;10:1586. doi: 10.3389/fphys.2019.01586. eCollection 2019.
Heme oxygenase (HO)-1 plays an important role during hibernation by catalyzing the degradation of heme to biliverdin/bilirubin, ferrous iron, and carbon monoxide, which activates the protective mechanisms against stress. In this context, it was important to analyze the metabolic processes of heme. Nevertheless, to date, no study has approached on biosynthesis of heme. Therefore, our study aims to understand the process of heme biosynthesis, which regulates cell survival in conditions of hypothermia and calorie restriction (CR). During hibernation, the mRNA levels of enzymes responsible for heme biosynthesis were increased in the liver tissue of a Syrian hamster model of hibernation. Moreover, heme trafficking and iron metabolism were found to be more active, as assessed based on the changes in the levels of heme transporter and ferroportin mRNA. The levels of HO-1, a powerful antioxidant, were also upregulated during hibernation. Additionally, increased levels of Sirt-1 mRNA were also observed. These enzymes are known to act as cellular metabolic sensors that activate the cytoprotective mechanisms. These results indicate that HO-1 induction, brought about by the upregulation of heme during the pre-hibernation period, may protect against external stress. Here, we describe heme catabolism during hibernation by analyzing the regulation of the key molecular players involved in heme metabolism. Therefore, this study offers a new strategy for the better regulation of intracellular heme concentrations during hypothermia and other stresses.
血红素加氧酶（HO）-1在冬眠过程中发挥着重要作用，它催化血红素降解为胆绿素/胆红素、亚铁离子和一氧化碳，从而激活应激保护机制。在此背景下，分析血红素的代谢过程十分重要。然而，迄今为止，尚无关于血红素生物合成的研究。因此，我们的研究旨在了解血红素生物合成过程，该过程在体温过低和卡路里限制（CR）条件下调节细胞存活。在冬眠期间，叙利亚仓鼠冬眠模型肝脏组织中负责血红素生物合成的酶的mRNA水平升高。此外，根据血红素转运蛋白和铁转运蛋白mRNA水平的变化评估发现，血红素运输和铁代谢更为活跃。强大的抗氧化剂HO-1的水平在冬眠期间也上调。此外，还观察到Sirt-1 mRNA水平升高。已知这些酶作为细胞代谢传感器激活细胞保护机制。这些结果表明，冬眠前期血红素上调导致的HO-1诱导可能抵御外部应激。在此，我们通过分析血红素代谢中关键分子参与者的调控来描述冬眠期间的血红素分解代谢。因此，本研究为在体温过低和其他应激期间更好地调节细胞内血红素浓度提供了一种新策略。
