At: https://www.frontiersin.org/articles/10.3389/fimmu. 2019.01824/full#supplementary-material
Cell. Mol. Life Sci. (2015) 72:983?97 DOI 10.1007/s00018-014-1730-Cellular and Molecular Life SciencesRESEARCH ARTICLEMitochondrial ferritin, a brand new target for inhibiting neuronal tumor cell proliferationZhen-Hua Shi ?Fang-Fang Shi ?Yue-Qi Wang ?Alex D. Sheftel ?Guangjun Nie ?Ya-Shuo Zhao ?Lin-Hao You ?Yu-Jing Gou ?Xiang-Lin Duan ?Bao-Lu Zhao ?Hong-Meng Xu ?Chun-Yan Li ?Yan-Zhong ChangReceived: 24 July 2014 / Revised: 3 September 2014 / Accepted: five September 2014 / Published on the web: 12 September 2014 ?The Author(s) 2014. This article is published with open Spiperone Epigenetic Reader Domain access at Springerlink.comAbstract Mitochondrial ferritin (FtMt) has a important effect on the regulation of cytosolic and mitochondrial iron levels. Having said that, because of the deficiency of iron regulatory elements (IRE) in FtMt’s gene sequence, the exact function of FtMt remains unclear. In the present study, we located that FtMt drastically inhibited SH-SY5Y cell proliferation and tumor growth in nude mice. Interestingly, excess FtMt didn’t adversely influence the development of drosophila. Also, we found that the expression of FtMt in human standard brain tissue was drastically higherZ.-H. Shi, F.-F. Shi and Y.-Q. Wang contributed equally to this function. Z.-H. Shi and F.-F. Shi are co-first authors.Electronic supplementary material The online version of this article (doi:ten.1007/s00018-014-1730-0) contains supplementary material, which is readily available to authorized users.Z.-H. Shi ?F.-F. Shi ?Y.-Q. Wang ?Y.-S. Zhao ?L.-H. You ?Y.-J. Gou ?X.-L. Duan ?B.-L. Zhao ?Y.-Z. Chang Crucial Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Science, Hebei Typical University, Shijiazhuang 050024, Hebei, China Z.-H. Shi e-mail: [email protected] Z.-H. Shi ?F.-F. Shi ?Y.-Q. Wang ?Y.-S. Zhao ?L.-H. You ?Y.-J. Gou ?X.-L. Duan ?B.-L. Zhao ?Y.-Z. Chang Crucial Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Standard University, Shijiazhuang 050024, Hebei, China Z.-H. Shi ?F.-F. Shi ?Y.-Q. Wang ?Y.-S. Zhao ?L.-H. You ?Y.-J. Gou ?X.-L. Duan ?B.-L. Zhao ?Y.-Z. Chang ( ) Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Standard University, Shijiazhuang 050024, Hebei, China e-mail: [email protected] that of neuroblastoma, but not higher than that of neurospongioma. Even so, the expression of transferrin receptor 1 is fully opposite. We thus hypothesized that enhanced expression of FtMt may perhaps negatively impact the vitality of neuronal tumor cells. Thus, we further investigated the DL-alpha-Tocopherol Biological Activity underlying mechanisms of FtMt’s inhibitory effects on neuronal tumor cell proliferation. As expected, FtMt overexpression disturbed the iron homeostasis of tumor cells and drastically downregulated the expression of proliferating cell nuclear antigen. Additionally, FtMt impacted cell cycle, causing G1/S arrest by modifying the expression of cyclinD1, cyclinE, Cdk2, Cdk4 and p21. Remarkably, FtMt strongly upregulated the expression of the tumor suppressors, p53 and N-myc downstream-regulated gene-1 (NDRG1), but significantly decreased C-myc, N-myc and p-Rb levels. This study demonstrates for the very first time a new function and mechanism for FtMt in theA. D. Sheftel University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON K1Y 4W7, Canada G. Nie CAS Key Laboratory for Biomedical Effects of Nanomaterial.