基本情報

所属

• 薬学研究院　創薬科学研究教育センター

職名

• 助教

学位

• 博士(理学)（東京工業大学）

J-Global ID

• 200901099156943384

研究キーワード

• 生物物理化学   

研究分野

• ライフサイエンス / 分子生物学

担当教育組織

•  学士課程　薬学部
•  修士課程　生命科学院

職歴

• 2007年04月 - 現在 北海道大学 薬学研究院 助教
• 1998年04月 - 2007年03月 北海道大学 薬学研究科 助手
• 1998年02月 - 1998年03月 北海道大学 薬学部 助手
• 1996年01月 - 1998年01月 北海道大学 薬学部 教務職員
• 1994年04月 - 1995年12月 日本学術振興会 特別研究員

学歴

• 1992年04月 - 1995年12月   東京工業大学   生命理工学研究科   バイオサイエンス専攻
• 1990年04月 - 1992年03月   東京工業大学   理工学研究科   生命理学専攻
• 1986年04月 - 1990年03月   東京工業大学   理学部   生命理学科

所属学協会

• 日本薬学会   

研究活動情報

論文

• Higher incidence of acute kidney injury in patients treated with piperacillin/tazobactam than in patients treated with cefepime: a single-center retrospective cohort study.

  Kadomura S, Takekuma Y, Sato Y, Sumi M, Kawamoto K, Itoh T, Sugawara M

  Journal of pharmaceutical health care and sciences 5 13 - 13 2019年 [査読有り][通常論文]
   

  Background: Piperacillin/tazobactam (PIPC/TAZ) and cefepime (CFPM) are commonly used for the treatment of nosocomial and healthcare-associated infections. Recent reports have suggested that the incidence of acute kidney injury (AKI) in patients treated with a combination of vancomycin (VCM) and PIPC/TAZ is higher than that in patients treated with CFPM. However, there have been few reports on a comparison of the incidences of AKI in patients treated with PIPC/TAZ monotherapy and patients treated with CFPM. In this study, we investigated whether the incidence of AKI in patients treated with PIPC/TAZ is higher than that in patients treated with CFPM. Methods: This study was a single-center retrospective observational study. Patients who died during the therapeutic period, patients younger than 18 years of age, and patients undergoing hemodialysis were excluded. Primary outcomes were the incidence of AKI and the AKIN stages defined by the Acute Kidney Injury Network. Secondary outcomes were discontinuation and/or change of antibiotics and initiation of dialysis due to AKI. We also investigated the time to onset and the risk factors of AKI in this population. Results: There were 163 patients in the PIPC/TAZ group and 103 patients in the CFPM group. The incidence of AKI in patients treated with PIPC/TAZ (8.6%) was significantly higher than that in patients treated with CFPM (0.9%) (odds ratio (OR), 9.53; 95% confidence interval (CI), 1.41-408; p= 0.011). AKI severity was mostly stage 1 in both groups. There was no discontinuation and/or changes of antibiotics and there was no initiation of dialysis in either group. The onset of AKI in the PIPC/TAZ group (median period of 4 days) was earlier than that in the CFPM group. PIPC/TAZ was determined to be an independent risk factor of AKI in multivariate analysis (adjusted OR, 9.56; 95% CI, 1.21-75.3; p = 0.032). Conclusions: This study showed that the incidence of AKI in patients who received PIPC/TAZ was higher than that in patients who received CFPM. Furthermore, the onset of AKI was earlier in patients who received PIPC/TAZ than in patients who received CFPM. PIPC/TAZ was an independent risk factor of AKI in this study population.
• An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1

  Yuto Takekawa, Yuki Sato, Yoshiaki Yamaki, Mei Imai, Kazuma Noto, Masato Sumi, Yoh Takekuma, Ken Iseki, Mitsuru Sugawara

  BIOLOGICAL & PHARMACEUTICAL BULLETIN 39 3 301 - 307 2016年03月 [査読有り][通常論文]
   

  Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. Recently, Niemann Pick Cl-Like 1 (NPC1L1) transporter was identified as being critical for cholesterol absorption. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. The uptake of lysophosphatidylcholine (LPC)-4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid saccinimidyl ester (BODIPY), a fluorescently labeled phospholipid, in lipid emulsion particles containing cholesterol (1 mu m) was significantly increased compared to that without cholesterol in Caco-2 cells. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 (CoQ10), by this mechanism. The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol.
• Difference in the Dissolution Behaviors of Tablets Containing Polyvinylpolypyrrolidone (PVPP) Depending on Pharmaceutical Formulation After Storage Under High Temperature and Humid Conditions

  Yoh Takekuma, Haruka Ishizaka, Masato Sumi, Yuki Sato, Mitsuru Sugawara

  JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES 19 4 511 - 519 2016年 [査読有り][通常論文]
   

  PURPOSE. Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone (PVPP) as a disintegrant. The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. METHODS. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodipheny lmethane, 2-aminobiphenyl, 2-(p-tolyl) benzoic acid or 4.4'-biphenol as principal agents, cellulose, lactose hydrate, PVPP and magnesium stearate as additives, were made by direct compression. The model tables were wrapped in paraffin papers and stored for 2 weeks at 40 degrees C/75% relative humidity (RH). Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. RESULTS. Model tablets with a simple composition were able to reproduce a decreased dissolution rate after storage at 40 degrees C/75% RH. These tablets showed significantly decreased water absorption activities after storage. In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution. 2-Benzylaniline tablets showed a remarkably decreased dissolution rate and 2-aminobiphenyl and 2-(p-tolyl) benzoic acid tablets showed slightly decreased dissolution rates, though 4,4'-biphenol tablets did not show a decrease dissolution rate. CONCLUSIONS. We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP. The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions.
• 開封後のスタチン製剤の安定性に及ぼす 光・温度・湿度の影響

  武隈 洋, 高地里佳, 石坂 悠, 佐藤夕紀, 鷲見正人, 菅原 満

  医療薬学 40 3 135 - 146 2015年 [査読有り][通常論文]
  
• Intracellular Uptake Mechanism of Lutein in Retinal Pigment Epithelial Cells

  Yuki Sato, Yu Kondo, Masato Sumi, Yoh Takekuma, Mitsuru Sugawara

  JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES 16 3 494 - 501 2013年 [査読有り][通常論文]
   

  Purpose. Lutein is a carotenoid mainly found in green leafy vegetables and is located in the macula lutea in the human eye. It has received much attention recently due to its preventive effect on age-related macular degeneration, and it has been consumed as a supplement. However, little information about the pharmacokinetic properties of lutein is available. Detailed knowledge of pharmacokinetic properties of lutein is needed for the development of pharmaceutics. In this study, we focused on the macular accumulation of lutein and investigated the uptake mechanism into human retinal pigment epithelial cells. Methods. ARPE-19 cells were used for the study on the accumulation mechanism of lutein. The concentration of lutein was determined using an HPLC system. Involvement of scavenger class B type 1 (SR-B1) in the accumulation of lutein in ARPE-19 cells was suggested from the results of an inhibition study using block lipid transport 1 (BLT-1), a selective inhibitor of SR-B1. To investigate the involvement of SR-B1 in more detail, small interfering RNA (siRNA) was transfected and the mRNA and protein expression levels of SR-B1 were assessed by quantitative real-time reverse transcription polymerase chain reaction and Western blotting, respectively. Results. We confirmed a sufficient siRNA knockdown effect in both mRNA and protein expression levels of SR-B1. We then found that lutein uptake was significantly decreased by siRNA knockdown of SR-B1. Conclusion. The uptake of lutein was significantly decreased by 40% compared with the control uptake level. This suggested that active transport of lutein into ARPE-19 cells is mainly via SR-B1, given the result that lutein uptake at 4 degrees C was about 40% less that that at 37 degrees C.
• Photo-induced proton transport of Pharaonis phoborhodopsin (sensory rhodopsin II) is ceased by association with the transducer

  Y Sudo, M Iwamoto, K Shimono, M Sumi, N Kamo

  BIOPHYSICAL JOURNAL 80 2 916 - 922 2001年02月 [査読有り][通常論文]
   

  Phoborhodopsin (pR; also sensory rhodopsin II, sRII) is a retinoid protein in Halobacterium salinarum and works as a receptor of negative phototaxis, Pharaonis phoborhodopsin (ppR; also pharaonis sensory rhodopsin II, psRII) is a corresponding protein of Natronobacterium pharaonis. In bacterial membrane, ppR forms a complex with its transducer pHtrII, and this complex transmits the light signal to the sensory system in the cytoplasm, We expressed pHtrII-free ppR or ppR-pHtrII complex in H. salinarum Pho81/wr(-) cells. Flash-photolysis experiments showed no essential changes between pHtrII-free ppR and the complex. Using SnO2 electrode, which works as a sensitive pH electrode, and envelope membrane vesicles, we showed the photo-induced outward proton transport. This membranous proton transport was also shown using membrane vesicles from Escherichia coli in which ppR was functionally expressed. On the other hand, the proton transport was ceased when ppR formed a complex with pHtrII, Using membrane sheet, it was shown that the complex undergoes first proton uptake and then release during the photocycle, the same as pHtrII-free ppR, although the net proton transport ceases. Taking into consideration that the complex of sRII (pR) and its transducer undergoes extracellular proton circulation (J. Sasaki and J. L. Spudich, 1999, Biophys. J. 77:2145-2152), we inferred that association with pHtrII closes a cytoplasmic channel of ppR, which lead to the extracellular proton circulation.
• Occurrence of D-amino acids and a pyridoxal 5 '-phosphate-dependent aspartate racemase in the acidothermophilic archaeon, Thermoplasma acidophilum

  ZQ Long, JA Lee, T Okamoto, M Sekine, N Nimura, K Imai, M Yohda, T Maruyama, M Sumi, N Kamo, A Yamagishi, T Oshima, H Homma

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 281 2 317 - 321 2001年02月 [査読有り][通常論文]
   

  Free D-amino acid content in some archaea was investigated and D-forms of several amino acids were found in them. in the acidothermophilic archaeon, Thermoplasma acidophilum, the proportion of D-aspartate (D-Asp) to total Asp was as high as 39.7%, Crude extracts of Thermoplasma acidophilum had Asp-specific racemase activity that was pyridoxal 5'-phosphate (PLP)-dependent. The relative insensitivity to a SH-modifying reagent distinguished this activity from those of the PLP-independent Asp racemases found in other hyperthermophilic archaea (Matsumoto, M,, ct at, J. Bacteriol. 181, 6560-6563 1999), Thus, high levels of D-Asp should be produced by a new type(s) of Asp-specific racemase in Thermoplasma acidophilum, although the function of D-Asp in this archaeon remains unknown. (C) 2001 Academic Press.
• 1P037高度好塩好アルカリ性菌走光性光受容タンパク質はホモ複合体形成能を持つ

  鷲見 正人

  生物物理 41 S42  一般社団法人 日本生物物理学会 2001年
• Effects of three characteristic amino acid residues of Pharaonis phoborhodopsin on the absorption maximum

  K Shimono, M Iwamoto, M Sumi, N Kamo

  PHOTOCHEMISTRY AND PHOTOBIOLOGY 72 1 141 - 145 2000年07月 [査読有り][通常論文]
   

  Phoborhodopsin (pR or sensory rhodopsin II, sRII) or pharaonis phoborhodopsin (ppR or pharaonis sensory rhodopsin II, psRII) has a unique absorption maximum (lambda(max)) compared with three other archaeal rhodopsins: lambda(max) of pR or ppR at ca 500 nm and others at 560-590 nm, Alignment of amino acid sequences revealed three sites characteristic of the shorter wavelength-absorbing pigments, The amino acids of these three sites are conserved completely among archaeal rhodopsins having longer lambda(max), and are different from those of pR or ppR, We replaced these amino acids of ppR with amino acids corresponding to those of bacteriorhodopsin, Val-108 to Met, Gly-130 to Ser and Thr-204 to Ala, The lambda(max) of V108M mutant was 502 nm with a slight redshift, G130S land T204A mutants had lambda(max) of 503 and 508 nm, respectively, Thus, each site contributes only a small effect to the color tuning. We then constructed three double mutants and one triple mutant. The opsin-shifts of these mutants suggest that Val-108 and Thr-204 or Gly-130 are synergistic, and that Gly-130 and Thr-204 work additively. Even in the triple mutant, the lambda(max) was 515 nm, an opsin-shift only ca 30% of the shift value from 500 to 560 nm. This means that there is another yet unidentified factor responsible for the color tuning.
• The M intermediate of Pharaonis phoborhodopsin is photoactive

  SP Balashov, M Sumi, N Kamo

  BIOPHYSICAL JOURNAL 78 6 3150 - 3159 2000年06月 [査読有り][通常論文]
   

  The retinal protein phoborhodopsin (pR) (also called sensory rhodopsin II) is a specialized photoreceptor pigment used for negative phototaxis in halobacteria, Upon absorption of light, the pigment is transformed into a short-wavelength intermediate, M, that most likely is the signaling state (or its precursor) that triggers the motility response of the cell. The M intermediate thermally decays into the initial pigment, completing the cycle of transformations. In this study we attempted to determine whether M can be converted into the initial state by light. The M intermediate was trapped by the illumination of a water glycerol suspension of phoborhodopsin from Natronobacterium pharaonis called pharaonis phoborhodopsin (ppR) with yellow light (>450 nm) at -50 degrees C. The M intermediate absorbing at 390 nm is stable in the dark at this temperature. We found, however, that M is converted into the initial (or spectrally similar) state with an absorption maximum at 501 nm upon illumination with 380-nm light at -60 degrees C. The reversible transformations ppR <-> M are accompanied by the perturbation of tryptophan(s) and probably tyrosine(s) residues, as reflected by changes in the UV absorption band. Illumination at lower temperature (-160 degrees C) reveals two intermediates in the photoconversion of M, which we termed M' (or M'(404)) and ppR' (or ppR'(496)). A third photoproduct, ppR'(504) is formed at -110 degrees C during thermal transformations of M'(404) and PPR'(496). The absorption spectrum of M'(404) (maximum at 404 nm) consists of distinct vibronic bands at 362, 382, 404, and 420 nm that are different from the vibronic bands of M at 348, 368, 390, and 415 nm. ppR'(496) has an absorption band that is shifted to shorter wavelengths by 5 nm compared to the initial ppR, whereas ppR'(504) is redshifted by at least 3 nm. As in bacteriorhodopsin, photoexcitation of the M intermediate of ppR and, presumably, photoisomerization of the chromophore during the M --> M' transition result in a dramatic increase in the proton affinity of the Schiff base, followed by its reprotonation during the M' --> ppR' transition. Because the latter reaction occurs at very low temperature, the proton is most likely taken from the counterion (Asp(75)) rather than from the bulk. The phototransformation of M reveals a certain heterogeneity of the pigment, which probably reflects different populations of M or its photoproduct M'. Photoconversion of the M intermediate provides a possible pathway for photoreception in halobacteria and a useful tool for studying the mechanisms of signal transduction by phoborhodopsin (sensory rhodopsin II).
• 2F1445 ファラオニスハロロドプシンの変異体タンパク質がクロライドイオン親和性に及ぼす影響

  金盛 竜朗, 岩本 真幸, 鷲見 正人, 加茂 直樹

  生物物理 40 S131  一般社団法人 日本生物物理学会 2000年
• 2F1500 ファラオニスフォボロドプシンの光照射プロトン輸送に対するトランスジューサ蛋白質の影響

  須藤 雄気, 岩本 真幸, 下野 和実, 鷲見 正人, 小山 行一, 加茂 直樹

  生物物理 40 S131  一般社団法人 日本生物物理学会 2000年
• Light-induced proton uptake and release of pharaonis phoborhodopsin detected by a photoelectrochemical cell

  M Iwamoto, K Shimono, M Sumi, K Koyama, N Kamo

  JOURNAL OF PHYSICAL CHEMISTRY B 103 46 10311 - 10315 1999年11月 [査読有り][通常論文]
   

  Phoborhodopsin (pR, also called sensory rhodopsin-IT, sR-II) is a receptor for the negative phototaxis of Halobacterium salinarum (pR), and pharaonis phoborhodopsin (ppR) is the corresponding receptor of Natronobacterium pharonis. pR and ppR are retinoid proteins and have a photocycle similar to that of bacteriorhodopsin. The photocycle of ppR in the millisecond time range includes M and O intermediates: ppR --> M --> O --> ppR. A photoelectrochemical cell was constructed composed of SnO2\thin ppR solution (similar to 50 mu M)\400 mM NaCl\SnO2. Photoinduced potential differences between two SnO2 transparent electrodes were measured. They were caused by changes in pH close to the SnO2 electrode surface. The signal was time-differentiated to envisage the direction of pH change and proton movement. A positive signal was due to a decrease in the local pH, i.e., proton release from ppR, and a negative signal was caused by the proton uptake. Immediately upon irradiation with continuous light, the transient negative on-response was observed for all pH examined. The shape of the off-response on turning off the light was pH-dependent: at alkaline or neutral pH, a negative component was observed followed by a positive component. The off-response was measured after the photosteady state was attained. The shape of the off-response well correlated with the ratio of contents of the M and O intermediates at the steady state. It is concluded that the proton uptake occurs during M --> O and the proton release during O --> ppR transitions.
• Positioning proton-donating residues to the Schiff-base accelerates the M-decay of pharaonis phoborhodopsin expressed in Escherichia coli

  M Iwamoto, K Shimono, M Sumi, N Kamo

  BIOPHYSICAL CHEMISTRY 79 3 187 - 192 1999年06月 [査読有り][通常論文]
   

  Phoborhodopsin (also called sensory rhodopsin II, sR-II) is a receptor for the negative phototaxis of Halobacterium salinarum (pR), and pharaonis phoborhodopsin (ppR) is the corresponding receptor of Natronobacterium pharaonis. pR and ppR are retinoid proteins and have a photocycle similar to that of bacteriorhodopsin (bR). A major difference between the photocycle of the ion pump bR and the sensor pR or ppR is found in their turnover rates which are much faster for bR. A reason for this difference might be found in the lack of a proton-donating residue to the Schiff base which is formed between the lysine of the opsin and retinal. To reconstruct a bR-like photochemical behavior, we expressed ppR mutants in Escherichia coli in which proton-donating groups have been reintroduced into the cytoplasmic proton channel. In measurement of the photocycle it could be shown that the F86D mutant of ppR (Phe86 was substituted by Asp) showed a faster decay of M-intermediate than the wild-type, which was even accelerated in the F86D/L40T double mutant. (C) 1999 Elsevier Science B.V. All rights reserved.
• 1PB038 高感度pH変化測定系を用いた光センサー蛋白質の光駆動型プロトン輸送活性の検討

  岩本 真幸, 下野 和実, 鷲見 正人, 小山 行一, 加茂 直樹

  生物物理 39 S79  一般社団法人 日本生物物理学会 1999年
• 1PB037 フォボロドプシン様蛋白質に特徴的な3ヶ所のアミノ酸残基がその極大吸収波長に及ぼす影響

  下野 和実, 岩本 真幸, 鷲見 正人, 加茂 直樹

  生物物理 39 S79  一般社団法人 日本生物物理学会 1999年
• Photoelectric response of halorhodopsin from Natronobacterium pharaonis

  K Koyama, M Sumi, N Kamo, JK Lanyi

  BIOELECTROCHEMISTRY AND BIOENERGETICS 46 2 289 - 292 1998年10月 [査読有り][通常論文]
   

  Halorhodopsin (hR) is an inward-directed light-driven chloride pump. This protein, from Natronobacterium pharaonis (abbreviated by phR), was immobilized on a transparent SnO2 electrode to construct a sandwich-type electrochemical cell. One of authors had previously reported photo-responses of a bacteriorhodopsin (bR)-immobilized cell [Photochem. Photobiol. 66:784 (1997)]. Unlike bR, the phR-immobilized photo-cell did not respond to illumination. Addition of azide anion, however, yielded photoresponses in a concentration-dependent manner. It was reported earlier that phR is capable of transporting proton in the presence of azide [Biochemistry 35:6604 (1996)]. The results we obtained confirm the notion that the photo-responses of this kind of cell originate from pH changes at the electrode interface. The pattern of the response in the presence of azide suggests that on illumination, phR first releases proton, followed by the proton uptake. This sequence is the same as that of wild bR. The response was decreased with increase in the concentration of halogen anions, as expected from competition for a binding site. (C) 1998 Elsevier Science S.A. All rights reserved.
• V108M mutant of pharaonis phoborhodopsin: Substitution caused no absorption change but affected its M-state

  K Shimono, M Iwamoto, M Sumi, N Kamo

  JOURNAL OF BIOCHEMISTRY 124 2 404 - 409 1998年08月 [査読有り][通常論文]
   

  Crystallographic data reveal that Met-118 in bacteriorhodopsin (bR) contacts directly with the C-9 methyl group of retinal, and Khorana et ad. [J. Biol. Chem, 268, 20305-20311 (1993)] suggest that this contact may regulate the absorption maximum (lambda(max)) We have replaced the amino acid (Val-108) corresponding to Met-118 of bR by methionine in pharaonis phoborhodopsin (ppR), whose lambda(max) is ca. 500 run, while those of other bacterial rhodopsins such as bR, halorhodopsin, and sensory rhodopsin are Fed-shifted by 60-90nm. By flash-photolysis measurement, we could not recognize a large spectral red-shift of the V108M mutant. On the other hand, the decay of ppR(M) (M-intermediate) of the mutant was approximately three times as fast as that of wild-type, and an M-like intermediate (M') whose lambda(max) is blue-shifted by 60 nm from that of M became appreciable, The replacement abolished the shoulder of the ppR(M) spectrum, From these findings, we infer that the distance between the retinal and the 108-position in ppR is relatively long, and that in the M-state this distance is shortened.
• Functional expression of pharaonis phoborhodopsin in Escherichia coli

  Kazumi Shimono, Masayuki Iwamoto, Masato Sumi, Naoki Kamo

  FEBS Letters 420 1 54 - 56 1997年12月22日 [査読有り][通常論文]
   

  Pharaonis phoborhodopsin, the photoreceptor of the negative phototaxis of archaebacterial Natronobacterium pharaonis, was functionally expressed in the heterologous system of Escherichia coli. Flash-photolysis on a millisecond time scale indicated that the photochemical properties of ppR expressed in E. coli were the same as those of the native ppR in N. pharaonis. We concluded that the integral membrane protein ppR is correctly folded in vivo in the eubacterial E. coli membrane.
• F0F1-ATPase genes from an archaebacterium, Methanosarcina barkeri

  M Sumi, M Yohda, Y Koga, M Yoshida

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 241 2 427 - 433 1997年12月 [査読有り][通常論文]
   

  It has been known that an archaebacterium Methanosarcina barkeri strain MS (DSM 800) has a V-type ATPase (Inatomi, K., et al. (1989) J. Biol. Chem. 264, 10954-10959). Here, we report cloning of a cluster of F0F1-ATPase genes from the same organism, the first ever found in archaebacteria. The cluster and encoded subunits exhibit several unusual features such that a gene for delta subunit is lacking, F-0-b subunit is unusually large, and gamma subunit is split into two peptide fragments. Attempts to detect F0F1-ATPase proteins and mRNA have been unsuccessful and therefore it is not certain if this gene cluster is really expressed in the cell. (C) 1997 Academic Press.
• Functional expression of pharaonis phoborhodopsin in Escherichia coli

  K Shimono, M Iwamoto, M Sumi, N Kamo

  FEBS LETTERS 420 1 54 - 56 1997年12月 [査読有り][通常論文]
   

  Pharaonis phoborhodopsin, the photoreceptor of the negative phototaxis of archaebacterial. Natronobacterium pharaonis, was functionally expressed in the heterologous system of Escherichia coli. Flash-photolysis on a millisecond time scale indicated that the photochemical properties of ppR expressed in E. coli were the same as those of the native ppR in N. pharaonis. Wt concluded that the integral membrane protein ppR is correctly folded in vivo in the eubacterial E, coli membrane. (C) 1997 Federation of European Biochemical Societies.
• Crystallization and preliminary X-ray characterization of chaperonin-60 from Paracoccus denitrificans

  TA Fukami, Y Takasuga, M Sumi, M Yohda, M Yoshida, K Miki

  JOURNAL OF CRYSTAL GROWTH 168 1-4 297 - 300 1996年10月 [査読有り][通常論文]
   

  Chaperonin-60 (cpn60) from Paracoccus denitrificans has been crystallized using polyethyleneglycol(PEG) 6000 and LiCl as precipitants. The crystals diffract up to 3.0 Angstrom resolution by using synchrotron radiation. They belong to the tetragonal space group P4(2)2(1)2 with unit cell parameters of a = b = 284 Angstrom, c = 152 Angstrom. Seven subunit molecules of cpn60 seem to exist in the asymmetric unit of the crystal. A complete diffraction data set was collected using a Weissenberg camera system attached to the synchrotron radiation source and merged up to 3.2 Angstrom resolution. Self-rotation functions calculated show the existence of a local 7-fold axis, suggesting the 7-fold symmetry ring assembly.
• A DNA FRAGMENT HOMOLOGOUS TO F1-ATPASE-BETA SUBUNIT WAS AMPLIFIED FROM GENOMIC DNA OF METHANOSARCINA-BARKERI - INDICATION OF AN ARCHAEBACTERIAL F-TYPE ATPASE

  M SUMI, MH SATO, K DENDA, T DATE, M YOSHIDA

  FEBS LETTERS 314 3 207 - 210 1992年12月 [査読有り][通常論文]
   

  A 490 bp DNA fragment was amplified from Methanosarcina barkeri genomic DNA by the polymerase chain reaction (PCR) using oligonucleotide primers designed based on conserved amino acid sequences of the F1-ATPase beta subunits. The amino acid sequence deduced from the DNA sequence of this fragment was highly homologous to a portion of the F1-ATPase beta subunit. This indicates that this archaebacterium has a gene of F-type ATPase in addition to a gene of V-type ATPase.
• Structure of holo-chaperonin studied with electron microscopy Oligomeric cpn10 on top of two layers of cpn60 rings with two stripes each

  Noriyuki Ishii, Hideki Taguchi, Masato Sumi, Masasuke Yoshida

  FEBS Letters 299 2 169 - 174 1992年03月09日 [査読有り][通常論文]
   

  A structural model of holo-chaperonin, known as a protein-folding control protein comprising 60 kDa (cpn60) and 10 kDa polypeptides (cpn10), is proposed based on the electron microscopic images of holo-chaperonin from Thermus thermophilus and cpn60 from Paracoccus denitrificans. Isolated Paracoccus cpn60 shows very similar images to those of Escherichia coli tetradecameric cpn60, a seven-membered ring in the top view and a rectangular shape with four stripes in the side view. However, a small number of half-thick rectangles with two stripes are also seen which indicates that a single cpn60-heptamer ring has two stripes parallel to the plane of the ring. Thermus holo-chaperonin shows a bullet-like shape in the side view, and antibory against cpn10 binds only to the round side of the bullet. We conclude that a single cpn60-heptamer ring with two stripes stacks into two layers, and a cpn10 oligomer binds to one side of the layers. © 1992.
• Identification and characterization of a chaperonin from Paracoccus denitrificans,

  Sumi M, Taguchi H, Yokoyama K, Ishii N, Yoshida M

  Biochem.(Life Sci. Adv.), 11 179 - 182 1992年 [査読有り][通常論文]
  

その他活動・業績

• Xenopus laevis oocytesを用いたNiemann-Pick C1-Like 1(NPC1L1)発現系の最適化

  八木 沙織, 梨本 俊亮, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 139年会 (4) 68 -68 2019年03月 [査読無し][通常論文]
  
• 肝遊離細胞サンドイッチ培養法を用いたカルベジロールの輸送および代謝における光学異性体間相互作用の解析

  伊藤 圭祐, 佐々木 萌子, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 138年会 (4) 51 -51 2018年03月 [査読無し][通常論文]
  
• 肝遊離細胞サンドイッチ培養法を用いたカルベジロールの輸送および代謝における光学異性体間相互作用の解析

  伊藤圭祐, 佐々木萌子, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 日本薬学会年会要旨集(CD-ROM) 138th (4) ROMBUNNO.27C‐am03 -51 2018年03月 [査読無し][通常論文]
  
• ヒトK562細胞に対するBCR-ABLチロシンキナーゼインヒビター(TKIs)Washout後持続的細胞増殖抑制効果の検証

  青山 剛, 武隈 洋, 佐藤夕紀, 鷲見正人, 菅原 満 第31回北海道TDM研究会研究発表会 2017年11月 [査読無し][通常論文]
  
• Continuous cytotoxic effects of BCR-ABL tyrosine kinase inhibitors (TKIs) after washout in human leukemic K562 cells.

  Aoyama T, Takekuma Y, Sumi M, Sato Y, Sugawara M 15th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology 2017年09月 [査読無し][通常論文]
  
• ルテインの製剤化による消化管吸収改善

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• 肝遊離細胞サンドイッチ培養法を用いたカルベジロールのグルクロン酸抱合反応に及ぼす光学異性体相互作用の評価

  佐々木萌子, 武隈洋, 佐藤夕紀, 鷲見正人, 菅原満 日本薬学会年会要旨集(CD-ROM) 137th (4) ROMBUNNO.25I‐am04 -63 2017年03月 [査読無し][通常論文]
  
• 慢性骨髄性白血病治療薬ダサチニブの消化管吸収に及ぼす消化管内pHおよびトランスポーターの影響

  助畑歩, 武隈洋, 鷲見正人, 佐藤夕紀, 菅原満 日本薬学会年会要旨集(CD-ROM) 137th (4) ROMBUNNO.25I‐pm06S -66 2017年03月 [査読無し][通常論文]
  
• 脂質異常症治療薬エゼチミブによるα-トコフェロールの消化管吸収抑制とその回避策-ラットおよびヒト血漿中濃度推移からのアプローチ-

  梨本俊亮, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原 満 第30回北海道TDM研究会研究発表会 2016年11月26日 [査読無し][通常論文]
  
• piperacillin/tazobactamとcefepimeの急性腎障害発症に関する後ろ向き観察 比較研究

  門村将太, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満, 福田由布子, 井藤達也 第30回北海道TDM研究会研究発表会 2016年11月26日 [査読無し][通常論文]
  
• 小腸コレステロールトランスポーターNPC1L1 (Niemann-Pick C1-Like 1)を介したCoenzyme Q10の消化管吸収改善

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• クロスポビドンを含む錠剤の製剤処方による溶出性の違い

  武隈洋, 石坂悠, 佐藤夕紀, 鷲見正人, 菅原満 日本医療薬学会年会講演要旨集(Web) 26 2016年
• TDMへの応用を目指した3種のチロシンキナーゼ阻害剤の血中濃度測定法の検証

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• Niemann-Pick C1 Like-1(NPC1L1)を標的とした乳剤化による難吸収性物質の吸収改善

  竹川 悠人, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 135年会 (4) 76 -76 2015年03月 [査読無し][通常論文]
  
• UDP-グルクロン酸転移酵素の生細胞と細胞破砕液での代謝活性の比較

  池上由麻, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第28回北海道TDM研究会研究発表会（札幌） 2014年11月29日 [査読無し][通常論文]
  
• UGT1A1 p.P364L変異体および UGT2B7 p.P366L変異体の光学異性体認識性

  依田めぐみ, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第28回北海道薬物作用談話会（札幌） 2014年07月19日 [査読無し][通常論文]
  
• 抗ウイルス薬 リバビリンのトランスポーターを介した消化管吸収の解析

  早風郁美, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第28回北海道薬物作用談話会（札幌） 2014年07月19日 [査読無し][通常論文]
  
• 中等量エトポシド(VP‐16)/シクロホスファミド(CY)/全身放射線(TBI)前処置レジメンにおけるVP‐16のPK/PD解析による投与量の最適化に関する検討

  田澤佑基, 武隈洋, 佐藤夕紀, 鷲見正人, 笠師久美子, 井関健, 菅原満 医療薬学フォーラム講演要旨集 22nd 242 2014年06月 [査読無し][通常論文]
  
• 細胞周期変化がエトポシド(VP-16)の殺細胞効果に与える影響

  田澤佑基, 吉岡美咲, 武隈 洋, 佐藤夕紀, 鷲見 正人, 菅原 満 日本薬学会北海道支部第141回例会（札幌） 2014年05月24日 [査読無し][通常論文]
  
• Coenzyme Q10の消化管吸収改善

  佐藤夕紀, 能登数馬, 竹川悠人, 鷲見正人, 武隈 洋, 菅原 満 特定非営利活動法人 日本コエンザイムQ 協会 第11回研究会プログラム（東京） 2014年01月28日 [査読無し][通常論文]
  
• Caco-2細胞におけるNPC1L1を介したコレステロール輸送の特徴

  阿部沙也華, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 第27回北海道TDM研究会研究発表会（札幌） 2013年11月30日 [査読無し][通常論文]
  
• 薬物曝露による細胞周期変化が細胞周期依存性の抗癌剤の作用に与える影響

  吉岡美咲, 田澤佑基, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 第27回北海道TDM研究会研究発表会（札幌） 2013年11月30日 [査読無し][通常論文]
  
• テアニンの体内動態および吸収機構の解明

  亀田佑生, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 第27回北海道TDM研究会研究発表会（札幌） 2013年11月30日 [査読無し][通常論文]
  
• 土-10-O14-09 乳剤化による難吸収性物質の吸収改善 : コレステロール輸送担体NPC1L1の利用(薬物動態,一般演題(口頭)14,再興、再考、創ろう最高の医療の未来)

  竹川 悠人, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本医療薬学会年会講演要旨集 23 219 -219 2013年08月28日
• 難吸収性ポリフェノールの乳剤化によるバイオアベイラビリティ改善

  星山博俊, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第27回北海道薬物作用談話会（江別） 2013年07月20日 [査読無し][通常論文]
  
• Niemann-pick C1 Like-1 (NPC1L1) を介した難吸収性物質の吸収改善へのアプローチ

  竹川悠人, 佐藤夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会北海道支部第140回例会（札幌） 2013年05月18日 [査読無し][通常論文]
  
• 熱力学的手法を用いた多剤排出輸送担体の基質探索の検討

  森岡悠紀, 鷲見正人, 佐藤夕紀, 武隈洋, 菅原満 日本薬学会北海道支部第140回例会（札幌） 2013年05月18日 [査読無し][通常論文]
  
• hOATPs/rOatps を介するミコフェノール酸グルクロナイドの輸送特性の種差

  坂本達彦, 鷲見正人, 佐藤夕紀, 武隈洋, 菅原満 日本薬学会北海道支部第140回例会（札幌） 2013年05月 [査読無し][通常論文]
  
• ヌクレオシドトランスポーターの基質輸送に及ぼすエトポシドの影響

  高田一輝, 田澤佑基, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 日本薬学会年会要旨集(CD-ROM) 133rd (4) ROMBUNNO.30P-AM13S -78 2013年03月 [査読無し][通常論文]
  
• 一包化調剤時におけるスタチン製剤の保存安定性

  高地里佳, 石坂悠, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 日本薬学会年会要旨集(CD-ROM) 133rd (4) ROMBUNNO.29PMF-389 -153 2013年03月 [査読無し][通常論文]
  
• シタラビンの白血病細胞内移行に対するエトポシドの影響

  高田一輝, 田澤佑基, 佐藤夕紀, 鷲見正人, 武隈洋, 菅原満 第26回北海道TDM研究会研究発表会（札幌） 2012年12月 [査読無し][通常論文]
  
• テアニンの脳移行に関与するトランスポーター

  川守田渉, 亀田佑生, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満 第26回北海道薬物作用談話会（札幌） 2012年07月 [査読無し][通常論文]
  
• P糖蛋白質(P‐gp)発現白血病由来細胞を用いたエトポシド(VP‐16)/シクロホスファミド(CY)曝露順序の殺細胞効果に及ぼす影響

  臼窪一平, 田澤佑基, 佐藤夕紀, 鷲見正人, 柴山良彦, 武隈洋, 菅原満 日本薬学会年会要旨集 132nd (4) 200 -200 2012年03月05日 [査読無し][通常論文]
  
• 中等量VP‐16/シクロホスファミド(CY)/全身放射線(TBI)前処置レジメンにおけるVP‐16のPK/PD解析

  田澤佑基, 松村一仙, 佐藤夕紀, 鷲見正人, 武隈洋, 重松明男, 笠師久美子, 山田武宏, 田中淳司, 橋野聡, 井関健, 今村雅寛, 菅原満 日本造血細胞移植学会総会プログラム・抄録集 34th 224 2012年02月01日 [査読無し][通常論文]
  
• エトポシド/シクロホスファミド併用の殺細胞効果に及ぼす曝露順序の影響 ～白血病由来 K-562 細胞及び P-糖タンパク質発現株を用いた検討～

  田澤佑基, 臼窪一平, 佐藤夕紀, 鷲見正人, 武隈 洋, 菅原 満 日本薬学会北海道支部第137回例会（札幌） 2011年12月 [査読無し][通常論文]
  
• 同種造血幹細胞移植時における中等量エトポシド(VP‐16)/シクロホスファミド(CY)/全身放射線(TBI)前処置レジメンの検討~VP‐16のPK/PD解析および培養細胞系を用いたVP‐16/CY曝露順序の検討~

  田澤佑基, 松村一仙, 佐藤夕紀, 鷲見正人, 武隈洋, 重松明男, 笠師久美子, 山田武宏, 井関健, 今村雅寛, 菅原満 TDM研究 28 (3) S203 -s203 2011年06月10日 [査読無し][通常論文]
  
• 白血病由来細胞を用いたエトポシド(VP‐16)/シクロホスファミド(CY)曝露順序の殺細胞効果への影響

  田澤佑基, 松村一仙, 笠師久美子, 佐藤夕紀, 鷲見正人, 武隈洋, 井関健, 菅原満 日本薬学会年会要旨集 131st (4) 178 -178 2011年03月05日 [査読無し][通常論文]
  
• テアニンの消化管吸収に関与するトランスポーター

  川守田 渉, 堀田 雄也, 佐藤 夕紀, 鷲見 正人, 武隈 洋, 菅原 満 日本薬学会年会要旨集 131年会 (4) 165 -165 2011年03月 [査読無し][通常論文]
  
• Light-induced reprotonation of the Schiff base in phoborhodopsin (sensory rhodopsin II)

  SP Balashov, M Sumi, N Kamo BIOPHYSICAL JOURNAL 78 (1) 474A -474A 2000年01月 [査読無し][通常論文]
  
• Temperature dependence of the kinetic isotope effect on the bacteriorhodopsin photocycle

  Chizhov, I, M Sumi, N Kamo, M Engelhard BIOPHYSICAL JOURNAL 76 (1) A242 -A242 1999年01月 [査読無し][通常論文]
  
• ファラオニスフォボロドプシンの変異蛋白質を用いた光中間体崩壊速度に関する研究

  岩本 真幸, 下野 和実, 鷲見 正人, 加茂 直樹 生物物理 38 (2) S88 1998年09月07日
• ファラオニスフォボロドプシンにおける極性アミノ酸が極大吸収波長に及ぼす影響

  下野 和実, 岩本 真幸, 鷲見 正人, 加茂 直樹 生物物理 38 (2) S138 1998年09月07日

共同研究・競争的資金等の研究課題

• ハロロドプシンのクロライド輸送機構解明と3量体形成の意義

  日本学術振興会：科学研究費補助金 (基盤研究(B))

  研究期間 : 2007年 -2009年 

  代表者 : 加茂 直樹
• 膜蛋白複合体における情報伝達機構:高度好塩菌の光受容を例として

  日本学術振興会：科学研究費補助金 (基盤研究(B))

  研究期間 : 2004年 -2006年 

  代表者 : 加茂 直樹
• 大腸菌走化性レセプタへの好塩菌走光性サブシステムの組み込み

  日本学術振興会：科学研究費補助金 (若手研究(B))

  研究期間 : 2004年 -2005年 

  代表者 : 鷲見 正人
• ハロバクテリアの走光性レセプターフォボロドプシンの生物物理化学的研究

  日本学術振興会：科学研究費補助金 (基盤研究(B))

  研究期間 : 2001年 -2003年 

  代表者 : 加茂 直樹
• 光駆動型塩化物イオンポンプ、ファラオニスハロロドプシンのプロトンポンプへの変換

  日本学術振興会：科学研究費補助金 (若手研究(B))

  研究期間 : 2001年 -2002年 

  代表者 : 鷲見 正人
• フォボロドプシン様光受容膜タンパク質の構造と機能

  日本科学協会：笹川研究助成

  研究期間 : 1998年04月 -1999年03月 

  代表者 : 鷲見 正人
• 光受容タンパク質・ファラオニスフォボロドプシンの構造と機能

  文部省：科学研究費補助金 (奨励研究(A))

  研究期間 : 1998年 -1999年 

  代表者 : 鷲見 正人
• 組み替え体を用いたフォボロドプシンの物理化学的研究

  文部省：科学研究費補助金 (基盤研究(B))

  研究期間 : 1998年 -1999年 

  代表者 : 加茂 直樹
• バクテリアの多剤薬物排出輸送体に関する生物物理化学的研究

  文部省：科学研究費補助金 (基盤研究(B))

  研究期間 : 1996年 -1996年 

  代表者 : 加茂 直樹
• 原核生物におけるV型、Ｆ型プロトン輸送ATPaseの分子進化と機能

  日本学術振興会：科学研究費補助金 (特別研究員奨励費)

  研究期間 : 1994年 -1995年 

  代表者 : 鷲見 正人
• molecular mechanism of photosignaling

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大学運営

委員歴

• 2016年06月 - 2018年03月   北海道TDM研究会   事務局