Establishment of the new strategy for accurate diagnosis of zinc deficiency

• Project/Area Number: 26660086
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied biochemistry
• Research Institution: Kyoto University
• Principal Investigator: Taiho Kambe 京都大学, 生命科学研究科, 准教授 (90303875)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 亜鉛欠乏 / 診断法 / 健康増進 / 超高齢社会 / 亜鉛要求性酵素

Outline of Final Research Achievements

In general, zinc deficiency is diagnosed by evaluation of serum zinc status. However, serum zinc status is altered by daily fluctuation or during inflammation, which may be a problem in the case that the accurate diagnosis is required for elderly people because they often suffer from various chronic diseases. Because, at present, Japan faces super-aged society at present, establishing the new strategy for accurate diagnosis of zinc deficiency is more important than ever.
In this study, I tried to establish such strategy by generating useful monoclonal antibody to detect proteins/enzymes whose expression is changed in response to zinc status. Moreover, I investigated zinc requiring enzyme activity whose activity was changed during zinc deficiency. I generated one antibody, which nicely detects zinc transporter in zinc-deficient dependent pattern, and one enzyme whose activity shows drastic change in response to zinc deficiency.

Research Products

• [Journal Article] Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency (2016)
  • Author(s): Itsumura N, Kibihara Y, Fukue K, Miyata A, Fukushima K, Tamagawa-Mineoka R, Katoh N, Nishito Y, Ishida R, Narita H, Kodama H, Kambe T
  • Journal Title: Pediatr Res Volume: 印刷中
  • NAID: 120006863495
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Activation of zinc-requiring ectoenzymes by ZnT transporters during the secretory process: Biochemical and molecular aspects (2016)
  • Author(s): Kambe T, Takeda T, Nishito Y
  • Journal Title: Arch Biochem Biophys Volume: ー Pages: 37-42
  • DOI: 10.1016/j.abb.2016.03.035
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Functions of Metallothionein and ZIP and ZnT Transporters: An Overview and Perspective (2016)
  • Author(s): Kimura T, Kambe T
  • Journal Title: Int J Mol Sci. Volume: 17 Issue: 3 Pages: 1-22
  • DOI: 10.3390/ijms17030336
  • NAID: 120005947123
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation (2016)
  • Author(s): Hashimoto A, Nakagawa M, Tsujimura N, Miyazaki S, Kizu K, Goto T, Komatsu Y, Matsunaga A, Shirakawa H, Narita H, Kambe T, Komai M
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 310 Issue: 5 Pages: R459-R468
  • DOI: 10.1152/ajpregu.00439.2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 亜鉛トランスポーターZIP4を標的とした亜鉛栄養の改善 (2016)
  • Author(s): 橋本彩子、神戸大朋
  • Journal Title: 亜鉛栄養治療 Volume: 印刷中
  • NAID: 40021096575
• [Journal Article] Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation. (2015)
  • Author(s): Yamada D, Saiki S, Furuya N, Ishikawa K, Imamichi Y, Kambe T, Fujimura T, Ueno T, Koike M, Sumiyoshi K, Hattori N
  • Journal Title: Biochem Biophys Res Commun. Volume: 471 Issue: 1 Pages: 109-116
  • DOI: 10.1016/j.bbrc.2016.01.171
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Overview of Inherited Zinc Deficiency in Infants and Children (2015)
  • Author(s): Kambe T, Fukue K, Ishida R, Miyazaki S
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 61 Issue: Supplement Pages: S44-S46
  • DOI: 10.3177/jnsv.61.S44
  • NAID: 130005109853
  • ISSN: 0301-4800, 1881-7742
  • Peer Reviewed / Open Access
• [Journal Article] Mg, Zn and Cu Transport Proteins: A Brief Overview from Physiological and Molecular Perspectives (2015)
  • Author(s): Hashimoto A, Kambe T.
  • Journal Title: Journal of Nutritional Science and Vitaminology Volume: 61 Issue: Supplement Pages: S116-S118
  • DOI: 10.3177/jnsv.61.S116
  • NAID: 130005109877
  • ISSN: 0301-4800, 1881-7742
  • Peer Reviewed / Open Access
• [Journal Article] Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting (2015)
  • Author(s): 2)Hashimoto, A., Ohkura, K., Takahashi, M., Kizu, K., Narita, H., Enomoto, S., Miyamae, Y., Masuda, S., Nagao, M., Irie, K., Ohigashi, H., Andrews, G. K., Kambe, T.
  • Journal Title: Biochemical Journal Volume: 472 Issue: 2 Pages: 183-193
  • DOI: 10.1042/bj20150862
  • NAID: 120006305978
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk. (2015)
  • Author(s): Kumar L, Michalczyk A, McKay J, Ford D, Kambe T, Hudek L, Varigios G, Taylor PE, Ackland ML.
  • Journal Title: Genes Nutr. Volume: 10 Issue: 5 Pages: 487-487
  • DOI: 10.1007/s12263-015-0487-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism. (2015)
  • Author(s): Kambe T, Tsuji T, Hashimoto A, Itsumura N.
  • Journal Title: Physiol Rev. Volume: 95 Pages: 749-84
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] なぜ亜鉛は生命に必要なのか？ 亜鉛生物学の潮流と今後の課題について (2015)
  • Author(s): 深田俊幸、神戸大朋
  • Journal Title: 細胞工学 Volume: 34 Pages: 310-316
• [Journal Article] Simple and Rapid Separation of Soyasaponin Bb from a Soy Extract (2015)
  • Author(s): H. Katano, N. Okamoto, M. Takakuwa, S. Taira, T. Kambe, M. Takahashi
  • Journal Title: Analytical Sciences Volume: 31 Issue: 2 Pages: 85-89
  • DOI: 10.2116/analsci.31.85
  • NAID: 130004827460
  • ISSN: 0910-6340, 1348-2246
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] EPO gene expression promotes proliferation, migration and invasion via the p38MAPK/AP-1/MMP-9 pathway by p21WAF1 expression in vascular smooth muscle cells (2015)
  • Author(s): Park SL, Won SY, Song JH, Kambe T, Nagao M, Kim WJ, Moon SK
  • Journal Title: Cell Signal Volume: 27 Issue: 3 Pages: 470-478
  • DOI: 10.1016/j.cellsig.2014.12.001
  • Peer Reviewed
• [Journal Article] Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis (2015)
  • Author(s): Kaneko M, Noguchi T, Ikegami S, Sakurai T, Kakita A, Toyoshima Y, Kambe T, Yamada M, Inden M, Hara H, Oyanagi K, Inuzuka T, Takahashi H, Hozumi I.
  • Journal Title: J Neurosci Res Volume: 93(2) Issue: 2 Pages: 370-9
  • DOI: 10.1002/jnr.23491
  • NAID: 120007100194
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular pathogenesis of spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins. (2014)
  • Author(s): Bin et al.
  • Journal Title: EMBO Molecular Medicine Volume: 6 Issue: 8 Pages: 1028-1042
  • DOI: 10.15252/emmm.201303809
  • Peer Reviewed
• [Journal Article] Methods to Evaluate Zinc Transport into and out of the Secretory and Endosomal-Lysosomal Compartments in DT40 Cells (2014)
  • Author(s): Kambe T
  • Journal Title: Methods Enzymol Volume: 534 Pages: 77-92
  • NAID: 120005359197
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 分泌経路で成熟する亜鉛要求性酵素活性化の分子機構 (2014)
  • Author(s): 神戸大朋、宮﨑志保
  • Journal Title: 日本応用酵素協会誌 Volume: 49 Pages: 9-15
• [Journal Article] 亜鉛栄養と亜鉛トランスポーター (2014)
  • Author(s): 神戸大朋
  • Journal Title: ビタミン Volume: 88 Pages: 560-564
  • Peer Reviewed
• [Journal Article] 亜鉛トランスポーターの特徴と生理機能 - ZIP, ZnTトランスポーターと細胞機能・疾患との関連性 - (2014)
  • Author(s): 辻徳治、神戸大朋
  • Journal Title: 生体の科学 Volume: 65 Pages: 370-378
  • NAID: 40020183766
  • Peer Reviewed
• [Journal Article] 食品と亜鉛－健康を保つための亜鉛摂取 (2014)
  • Author(s): 橋本彩子、神戸大朋
  • Journal Title: Functional Food Volume: 25 Pages: 48-51
  • Peer Reviewed
• [Journal Article] Current understanding of ZIP and ZnT zinc transporters in human health and diseases (2014)
  • Author(s): Kambe T, Hashimoto A, Fujimoto S.
  • Journal Title: Cellular and Molecular Life Sciences Volume: 71 Issue: 17 Pages: 3281-3295
  • DOI: 10.1007/s00018-014-1617-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Zinc Signaling: Conclusion (2016)
  • Author(s): Taiho Kambe
  • Organizer: The 93rd Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌）
  • Year and Date: 2016-03-22
  • Invited
• [Presentation] 亜鉛トランスポーターの機能と 亜鉛バイオロジー (2016)
  • Author(s): 神戸大朋
  • Organizer: 【理科大総合研究院バイオオルガノメタリクス研究部門】 研究交流集会
  • Place of Presentation: 東京理科大学（東京・東京）
  • Year and Date: 2016-03-17
  • Invited
• [Presentation] Zinc Signaling and Zinc Homeostasis: Conclusion (2015)
  • Author(s): Taiho Kambe
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（神戸・兵庫）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] How are zinc-requiring enzymes activated by zinc transporters in the early secretory pathway? (2015)
  • Author(s): Taiho Kambe
  • Organizer: 8th FAOPS Congress in Bangkok
  • Place of Presentation: バンコク（タイ）
  • Year and Date: 2015-11-24
  • Int'l Joint Research / Invited
• [Presentation] How are zinc-requiring ectoenzymes activated by zinc transporters in the secretory pathway? (2015)
  • Author(s): Taiho Kambe
  • Organizer: The 65th Conference of Japan Society of Coordination Chemistry
  • Place of Presentation: 奈良女子大学（奈良・奈良）
  • Year and Date: 2015-09-21
  • Invited
• [Presentation] Activation Mechanism of Zinc-Dependent Ectoenzymes by ZnT Zinc Transporters (2015)
  • Author(s): Taiho Kambe
  • Organizer: Gordon Research Conference, Cell Biology of Metals
  • Place of Presentation: バーモント州マウントスノー（アメリカ）
  • Year and Date: 2015-07-28
  • Int'l Joint Research / Invited
• [Presentation] 亜鉛動態におけるメタロチオネインの役割 (2015)
  • Author(s): 神戸大朋
  • Organizer: 第42回日本毒性学会学術年会
  • Place of Presentation: ポルテ金沢（金沢・石川）
  • Year and Date: 2015-06-30
  • Invited
• [Presentation] Zinc transporters and zinc deficiency of infants and children (2015)
  • Author(s): Taiho Kambe
  • Organizer: 12th Asian Congress of Nutrition (12th ACN)
  • Place of Presentation: パシフィコ横浜（横浜・神奈川）
  • Year and Date: 2015-05-17
  • Invited
• [Presentation] The roles of zinc transporters in zinc absorption and zinc physiology (2015)
  • Author(s): Taiho Kambe
  • Organizer: 12th Asian Congress of Nutrition (12th ACN)
  • Place of Presentation: パシフィコ横浜（横浜・神奈川）
  • Year and Date: 2015-05-15
  • Invited
• [Presentation] 亜鉛トランスポーター 亜鉛恒常性を制御するしくみ (2015)
  • Author(s): 神戸大朋
  • Organizer: ＜第29回日本医学会総会サテライトシンポジウム＞ 近畿亜鉛栄養治療研究会5周年記念・公開講座
  • Place of Presentation: 京都センチュリーホテル（京都・京都）
  • Year and Date: 2015-04-10
  • Invited
• [Presentation] How are zinc-requiring enzymes activated by zinc transporters in the early secretory pathway? (2014)
  • Author(s): Taiho Kambe
  • Organizer: AsBIC7, 7th Asian Biological Inorganic Chemistry Conference
  • Place of Presentation: Gold Coast (Australia)
  • Year and Date: 2014-12-04
  • Invited
• [Presentation] ZnT and ZIP: Essential zinc transporters for zinc transporters for zinc physiology and biochemistry (2014)
  • Author(s): Taiho Kambe
  • Organizer: Liaison Laboratory regular seminar, Institute of Molecular Embryology and Genetics, Kumamoto University
  • Place of Presentation: Kumamoto
  • Year and Date: 2014-11-05
  • Invited
• [Presentation] How do zinc transporters play their specific roles in cellular and physiological processes? (2014)
  • Author(s): Taiho Kambe
  • Organizer: The 86th Annual Meeting of the Japanese Biochemical Society 2014
  • Place of Presentation: Kyoto
  • Year and Date: 2014-10-17
• [Presentation] 亜鉛トランスポーターから視た亜鉛バイオロジー ～亜鉛の化学特性から欠乏性皮膚炎まで～ (2014)
  • Author(s): 神戸大朋
  • Organizer: 山梨皮膚疾患セミナー
  • Place of Presentation: 山梨
  • Year and Date: 2014-09-29
  • Invited
• [Presentation] THE COORDINATED FUNCTIONS OF ZNT TRANSPORTERS IN THE ACTIVATION OF ZINC-REQUIRING ENZYMES (2014)
  • Author(s): Taiho Kambe
  • Organizer: The 4th International Society of Zinc Biology Meeting
  • Place of Presentation: Asilomar (USA)
  • Year and Date: 2014-09-15
• [Presentation] 分泌経路において機能する亜鉛トランスポーター (2014)
  • Author(s): 神戸大朋
  • Organizer: 第25回日本微量元素学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-07-03
  • Invited
• [Presentation] 分泌経路の機能維持を担う亜鉛トランスポーター (2014)
  • Author(s): 神戸大朋
  • Organizer: 第9回トランスポーター研究会年会/JTRA2014
  • Place of Presentation: 名古屋
  • Year and Date: 2014-06-15
  • Invited
• [Presentation] 亜鉛栄養と亜鉛トランスポーター (2014)
  • Author(s): 神戸大朋
  • Organizer: 日本ビタミン学会第６６回大会
  • Place of Presentation: 姫路
  • Year and Date: 2014-06-14
  • Invited
• [Presentation] 乳児亜鉛欠乏予防基盤確立のためのZnT2遺伝子一塩基多型の影響評価 (2014)
  • Author(s): 神戸大朋、黍原祥恵、逸村直也、成田宏史、児玉浩子
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 北海道
  • Year and Date: 2014-05-31
• [Book] Zinc Signals in Cellular Functions and Disorders (2014)
  • Author(s): Fukada T, Kambe T
  • Publisher: Tokyo: Springer