Department of Biology, Institute of Biochemistry, Carleton University, Ottawa, ON, Canada.
Department of Biological Sciences and Center for Environmental Epigenetics and Development, University of Toronto, Toronto, ON, Canada.
Protein J. 2021 Feb;40(1):87-107. doi: 10.1007/s10930-020-09944-7. Epub 2021 Jan 2.
Mitochondria was long thought to be an "end function" organelle that regulated the metabolic flux and apoptosis in the cell. However, with the discovery of the mitochondrial peptide (MDP) humanin (HN/MTRNR2), the cytoprotective and pro-survival applications of MDPs have taken the forefront of therapeutic and diagnostic research. However, the regulation of humanin-like MDPs in natural model systems that can tolerate lethal environmental and cytotoxic insults remains to be investigated. Red-eared sliders are champion anaerobes that can withstand three continuous months of anoxia followed by rapid bouts of oxygen reperfusion without incurring cellular damage. Freshwater turtles employ extensive physiological and biochemical strategies to combat anoxia, with metabolic rate depression and a global enhancement of antioxidant and cytoprotective pathways being the two most important contributors. The main aim of this study was to uncover and characterize the humanin-homologue in freshwater turtles as well as investigate the differential regulation of humanin in response to short and long-term oxygen deprivation. In this study we have used de novo and homology-based protein modelling to elucidate the putative structure of humanin in red-eared sliders as well as an ELISA and western immunoblotting to confirm the protein abundance in the turtle brain and six peripheral tissues during control, 5 h, and 20 h anoxia (n = 4/group). We found that a humanin-homologue (TSE-humanin) is present in red-eared sliders and it may play a cytoprotective role against oxidative damage.
线粒体长期以来被认为是一种“终末功能”细胞器，调节细胞中的代谢通量和细胞凋亡。然而，随着线粒体肽（MDP）人胰岛素（HN/MTRNR2）的发现，MDP 的细胞保护和生存促进应用已成为治疗和诊断研究的前沿。然而，在能够耐受致命环境和细胞毒性损伤的天然模型系统中，人胰岛素样 MDP 的调节仍有待研究。红耳龟是冠军厌氧菌，能在缺氧 3 个月后连续耐受，随后迅速进行氧气再灌注，而不会造成细胞损伤。淡水龟采用广泛的生理和生化策略来对抗缺氧，代谢率下降和抗氧化和细胞保护途径的全面增强是两个最重要的贡献者。本研究的主要目的是揭示并鉴定淡水龟中的人胰岛素同源物，并研究人胰岛素在应对短期和长期缺氧时的差异调节。在这项研究中，我们使用从头和基于同源性的蛋白质建模来阐明红耳龟中人胰岛素的假定结构，以及 ELISA 和 Western 免疫印迹来确认在控制、5 小时和 20 小时缺氧期间（n = 4/组）在龟脑中的蛋白丰度和 6 种外周组织。我们发现红耳龟中存在人胰岛素同源物（TSE-humanin），它可能在对抗氧化损伤方面发挥细胞保护作用。
