Prof. Kiyono recieved the academic award of the pharmaceutical society of Japan, division of pharmaceutical health sciences and environmental toxicology.
2022/4/1
2022fy started
Members and publication list are updated.
2022/1/27
Published!
Three papers published in 2021 are added to the list.
2022/1/26
Thesis presentation of 4yr-bachelor course
Four presentations from the lab. Well done!
2022/1/26
English pages launched!
For non-Japanese-speakers, we are launching this English version.
Research
- Scope and achievement -
Our laboratory conducts research and education on the toxicology of environmental pollutants (mainly methylmercury and toxic heavy metals) and biotechnology for bio/phyto-remediation of metal-contaminated environments. We study mammalian cultured-cells, mice, Arabidopsis (plant model), and bacteria. And this is a major unique feature of the lab. See the publication list for our achievement. You may also check a message from Prof. Kiyono (in Japanese) with a translation tool.
We have four working groups:
>>>Takanezawa group molecular toxicology of methylmercury and toxic metals in mammalian cells keywords: autophagy, p62, ubiquitination, ER-stress
>>> Nakamura group toxicology of methylmercury in mice and evaluation of natural compounds as anti-MeHg drugs keywords: central nural dysfunction, behavioral test, oleanolic acid, anti-MeHg natural compounds
>>> Uraguchi group molecular genetics of toxic metal homeostasis in model plant Arabidopsis and molecular breeding of transgenic plants for phytoremediation keywords: root apical meristem, phytochelatin, DNA damage, cell-type specific promoter
>>> Ohshiro-Sone group
characterization of bacterial mercury-resistant transporter genes keywords: mer operon, mercury transporter, MerC, rare metals
Outlines of each research topic are availabe from the panels below (Sorry, only in Japanese at the moment).
Lab members (FY2021). Full lists of students and almumi are available at here in Japanese. Please note that "@" within the mail-link below is replaced by "-at-" to avoid spam mails.
Master course: 5 students, Undergraduate: 6th-grade of 6-yr course students (13 students), 5th-grade of 6yr course (13 students), 4th-grade of 4-yr course (4 students).
About Lab
- the lab at glance -
Faculty members
from front row left: Kiyono，Ohshiro-Sone，from back row left:Takanezawa, Uraguchi, Nakamura
Lectures and practical classes in charge
Public health I (1st semester, 3rd grade） Public health II（1st semester, 4th grade) Health Science（1st semester, 2nd grade) Public Health practical class（2nd semester, 3rd grade)
Uraguchi S, Ohshiro Y, Otsuka Y, Wada E, Naruse F, Sugaya K, Nagai K, Wongkaew A, Nakamura R, Takanezawa Y, Clemens S, Ohkama-Ohtsu, Kiyono M. Phytochelatin-mediated metal detoxification pathway is crucial for an organomercurial phenylmercury tolerance in Arabidopsis. Plant Molecular Biology (2022). https://doi.org/10.1007/s11103-021-01221-0
Nakamura R, Takanezawa Y, Ohshiro Y, Uraguchi S, Kiyono M. Effects of chemical forms of gadolinium on the spleen in mice after single intravenous administration. Biochemistry and Biophysics Reports, 29:101217 (2022) https://doi.org/10.1016/j.bbrep.2022.101217
Uraguchi S, Nagai K, Naruse F, Otsuka Y, Ohshiro Y, Nakamura R, Takanezawa Y, Kiyono M. Development of affinity bead–based in vitro metal–ligand binding assay reveals dominant cadmium affinity of thiol-rich small peptides phytochelatins beyond glutathione. Metallomics, 13:mfab068 (2021) https://doi.org/10.1093/mtomcs/mfab068
Takanezawa Y, Nakamura R, Sugimoto T, Ohshiro Y, Uraguchi S, Kiyono M. p62/sequestosome 1 attenuates methylmercury-induced endoplasmic reticulum stress in mouse embryonic fibroblasts. Toxicology Letters, 353:93-99 (2021) https://doi.org/10.1016/j.toxlet.2021.10.008
Ohshiro Y, Uraguchi S, Nakamura R, Takanezawa Y, Kiyono M. Cadmium transport activity of four mercury transporters (MerC, MerE, MerF and MerT) and effects of the periplasmic mercury-binding protein MerP on Mer-dependent cadmium uptake. FEMS Microbiology Letters, 367:fnaa177 (2020) https://doi.org/10.1093/femsle/fnaa177
Deromachi Y, Uraguchi S, Kiyono M, Kuga K, Nishimura K, Sato M-H, Hirano T. Stable expression of bacterial transporter ArsB attached to SNARE molecule enhances arsenic accumulation in Arabidopsis. Plant Signaling & Behavior, 15:11 (2020) https://doi.org/10.1080/15592324.2020.1802553
Uraguchi S, Ohshiro Y, Otsuka Y, Tsukioka H, Yoneyama N, Sato H, Hirakawa M, Nakamura R, Takanezawa Y, Kiyono M. Selection of Agar Reagents for Medium Solidification Is a Critical Factor for Metal (loid) Sensitivity and Ionomic Profiles of Arabidopsis thaliana. Frontiers in Plant Science, 11: 503 (2020) https://doi.org/10.3389/fpls.2020.00503
Takanezawa Y, Nakamura R, Kusaka T, Ohshiro Y, Uraguchi S, Kiyono M. Significant contribution of autophagy in mitigating cytotoxicity of gadolinium ions. Biochemical and Biophysical Research Communications, 526:206-212 (2020) https://doi.org/10.1016/j.bbrc.2020.03.080
Nakamura R, Shirahata T, Katsumi T, Konishi N, Takanezawa Y, Ohshiro Y, Uraguchi S, Kobayashi Y, Kiyono M. Oleanolic Acid-3-(1′2′Orthoacetate-Glucoside)-28-Glucoside Alleviates Methylmercury Toxicity in Vitro and in Vivo. BPB Reports, 2:56-60. (2019) https://www3.e-kenkyu.com/bpb-reports-online-journal/papers/17
Takanezawa Y, Nakamura R, Matsuda H, Yagi T, Egawa Z, Sone Y, Uraguchi S, Adachi T, Kiyono M. Intracellular Demethylation of Methylmercury to Inorganic Mercury by Organomercurial Lyase (MerB) Strengthens Cytotoxicity. Toxicological Science, 170:438-451. (2019) doi: 10.1093/toxsci/kfz094
Uraguchi S, Sone Y, Yoshikawa A, Tanabe M, Sato H, Otsuka Y, Nakamura R, Takanezawa Y, Kiyono M.SCARECROW promoter-driven expression of a bacterial mercury transporter MerC in root endodermal cells enhances mercury accumulation in Arabidopsis shoots. Planta, 250: 667-674. (2019) https://doi.org/10.1007/s00425-019-03186-3
Uraguchi S, Sone Y, Kamezawa M, Tanabe M, Hirakawa M, Nakamura R, Takanezawa Y, Kiyono M.Ectopic expression of a bacterial mercury transporter MerC in root epidermis for efficient mercury accumulation in shoots of Arabidopsis plants. Scientific Reports, 9:4347. (2019) doi: 10.1038/s41598-019-40671-x.
Takanezawa Y, Nakamura R, Sone Y, Uraguchi S, Kiyono M. An autophagy deficiency promotes methylmercury-induced multinuclear cell formation. Biochemical and Biophysical Research Communications, 511:460-467. (2019) doi: 10.1016/j.bbrc.2019.02.084
Nakamura R, Shirahata T, Konishi N, Takanezawa Y, Sone Y, Uraguchi S, Kobayashi Y, Kiyono M. Oleanolic acid 3-glucoside, a synthetic oleanane-type saponin, alleviates methylmercury toxicity in vitro and in vivo. Toxicology, 417:15-22. (2019) doi: 10.1016/j.tox.2019.02.006
Takanezawa Y, Nakamura R, Hamaguchi M, Yamamoto K, Sone Y, Uraguchi S, Kiyono M. Docosahexaenoic acid enhances methylmercury-induced endoplasmic reticulum stress and cell death and eicosapentaenoic acid potentially attenuates these effects in mouse embryonic fibroblasts. Toxicology Letter, 306:35-42. (2019) doi: 10.1016/j.toxlet.2019.02.009
Takanezawa Y, Nakamura R, Kojima Y, Sone Y, Uraguchi S, Kiyono M. Cytochalasin E increased the sensitivity of human lung cancer A549 cells to bortezomib via inhibition of autophagy. Biochemical and Biophysical Research Communications, 498: 603-608. (2018) doi: 10.1016/j.bbrc.2018.03.029.
Uraguchi S, Sone Y, Ohta Y, Ohkama-Ohtsu N, Hofmann C, Hess N, Nakamura R, Takanezawa Y, Clemens S, Kiyono M. Identification of C-terminal regions in Arabidopsis thaliana phytochelatin synthase 1 specifically involved in activation by arsenite. Plant and Cell Physiology, 59: 500-509. (2018) doi: 10.1093/pcp/pcx204.
清野正子. 薬学と磁気の接点. 磁気と健康, 29: 18-21. (2017)
Sone Y, Uraguchi S, Takanezawa Y, Nakamura R, Pan-Hou H, Kiyono M. Cysteine and histidine residues are involved in Escherichia coli Tn21 MerE methylmercury transport. FEBS Open Bio, 7: 1994-1999. (2017) DOI: 10.1002/2211-5463.12341
Takanezawa Y, Nakamura R, Harada R, Sone Y, Uraguchi S, Kiyono M. Sequestosome1/p62 protects mouse embryonic fibroblasts against low-dose methylmercury-induced cytotoxicity and is involved in clearance of ubiquitinated proteins. Scientific Reports 494: 641-647. (2017) doi: 10.1038/s41598-017-17112-8
Takanezawa Y, Nakamura R, Sone Y, Uraguchi S, Kobayashi K, Tomoda H, Kiyono M. Variation in the activity of distinct cytochalasins as autophagy inhibitiors in human lung A549 cells. Biochem Biophys Res Commun 494: 641-647. (2017) doi: 10.1016/j.bbrc.2017.10.135
Uraguchi S, Tanaka N, Hofmann C, Abiko K, Ohkama-Ohtsu N, Weber M, Kamiya T, Sone Y, Nakamura R, Takanezawa Y, Kiyono M, Fujiwara T, Clemens S. Phytochelatin Synthase has Contrasting Effects on Cadmium and Arsenic Accumulation in Rice Grains. Plant and Cell Physiology 58: 1730-1742. (2017) doi: 10.1093/pcp/pcx114
Sone Y, Uraguchi S, Takanezawa Y, Nakamura R, Pan-Hou H, Kiyono M.
A Novel Role of MerC in Methylmercury Transport and Phytoremediation of Methylmercury Contamination. Biological and Pharmaceutical Bulletin 40: 1125-1128. (2017) doi: 10.1248/bpb.b17-00213
Takanezawa Y, Nakamura R, Sone Y, Uraguchi S, Kiyono M. Atg5-dependent autophagy plays a protective role against methylmercury-induced cytotoxicity. Toxicology Letter 262: 135-141 (2016) doi: 10.1016/j.toxlet.2016.09.007
Nakamura R, Takanezawa Y, Sone Y, Uragchi S, Sakabe K, Kiyono K. Immunotoxic effect of low-dose methylmercury Is negligible in mouse models of ovalbumin or mite-induced Th2 allergy. Biological and Pharmaceutical Bulletin 39: 1353-1358 (2016) doi: 10.1248/bpb.b16-00306
Nakamura R, Sugano M, Sone Y, Sakabe K, Itoh T, Kiyono M. Establishment and characterization of human lymphatic endothelial cell line. Biological and Pharmaceutical Bulletin, 37:683-7 (2014)
Sone Y, Nakamura R, Pan-Hou H, Sato MH, Itoh T, Kiyono M. Increase methylmercury accumulation in Arabidopsis thaliana expressing bacterial broad-spectrum mercury transporter MerE. AMB Express, 3:52 (2013) doi: 10.1186/2191-0855-3-52
Sone Y, Nakamura R, Pan-Hou H, Itoh T, Kiyono M. Role of MerC, MerE, MerF, MerT, and/or MerP in resistance to mercurials and the transport of mercurials in Escherichia coli. Biological and Pharmaceutical Bulletin, 36:1835-41 (2013)
Sone Y, Mochizuki Y, Koizawa K, Nakamura R, Pan-Hou H, Itoh T, Kiyono M. Mercurial-resistance determinants in Pseudomonas strain K-62 plasmid pMR68. AMB Express, 3:41 (2013) doi: 10.1186/2191-0855-3-41
Kiyono M, Oka Y, Sone Y, Nakamura R, Sato MH, Sakabe K, Pan-Hou H. Bacterial heavy metal transporter MerC increases mercury accumulation in Arabidopsis thaliana. Biochem Eng J, 71:19-24 (2013) doi: 10.1016/j.bej.2012.11.007.
一方、自然界には、毒性の強い水銀化合物に対して耐性を示す細菌が存在します。その細菌が示す水銀耐性は、plasmid あるいは transposon 上に存在する機能の異なる複数の水銀耐性遺伝子により構成される水銀耐性オペロン (mer operon) により支配されます (Fig.1)。菌体外の無機水銀 (Hg2+) は、細胞間隙に存在する水銀結合因子 MerP に結合した後、水銀トランスポーターである MerT や MerC に受け渡され、菌体内に取り込まれます。菌体内に取り込まれた Hg2+ をレダクターゼである MerA により還元し、金属水銀 (Hg0) として菌体外に放出することで細菌は水銀耐性を獲得していると考えられています。