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Article ; Online: External K

Ishihara, Keiko

2018 Volume 150, Issue 7, Page(s) 977–989

Abstract: Strong inward rectifier K ...

Abstract	Strong inward rectifier K
MeSH term(s)	Action Potentials ; Animals ; Extracellular Space/metabolism ; HEK293 Cells ; Humans ; Ion Transport ; Mice ; Potassium/metabolism ; Potassium Channels, Inwardly Rectifying/metabolism ; Sodium/metabolism
Chemical Substances	Potassium Channels, Inwardly Rectifying ; Sodium (9NEZ333N27) ; Potassium (RWP5GA015D)
Language	English
Publishing date	2018-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3118-5
ISSN	1540-7748 ; 0022-1295
ISSN (online)	1540-7748
ISSN	0022-1295
DOI	10.1085/jgp.201711936
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Article ; Online: Clinical significance of human endogenous retrovirus K (HERV-K) in multiple myeloma progression.

Masuda, Yuta / Ishihara, Rei / Murakami, Yuki / Watanabe, Saki / Asao, Yuta / Gotoh, Nanami / Kasamatsu, Tetsuhiro / Takei, Hisashi / Kobayashi, Nobuhiko / Saitoh, Takayuki / Murakami, Hirokazu / Handa, Hiroshi

International journal of hematology

2022 Volume 117, Issue 4, Page(s) 563–577

Abstract: ... the association between HERVs and multiple myeloma (MM) progression. We found that HERV-K envelope (env) and long ... than in monoclonal gammopathy of undetermined significance or controls. HERV-K env knockdown increased proliferation in the MM ... CDKN1A were highly expressed in MM, and their expression was correlated with HERV-K expression. HERV-K ...

Abstract	Human endogenous retroviruses (HERVs) are retrotransposons that infect human germline cells and occupy 5-8% of the human genome. Their expression, though inhibited by mutation, deletion, and epigenetic mechanisms under normal conditions, is associated with diseases including cancer. This study aimed to clarify the association between HERVs and multiple myeloma (MM) progression. We found that HERV-K envelope (env) and long-term repeat (LTR) expression was statistically significantly higher within plasma cells in MM than in monoclonal gammopathy of undetermined significance or controls. HERV-K env knockdown increased proliferation in the MM.1S cell line and decreased the expression of the tumor suppressor genes TP53 and CDKN1A. TP53 and CDKN1A were highly expressed in MM, and their expression was correlated with HERV-K expression. HERV-K knockdown reduced apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3F, 3G, and 3H expression by 10-20% in MM.1S cells. The anti-retroviral agents nevirapine and nelfinavir suppressed proliferation and increased HERV-K expression in MM cell lines. Our results suggest that HERV-K is involved in MM progression, but its role is likely to go beyond promoting cell proliferation. Clarifying the role of HERV-K in MM will lead to the discovery of novel treatment strategies and supply new insights into MM pathogenesis.
MeSH term(s)	Humans ; Endogenous Retroviruses/genetics ; Multiple Myeloma/genetics ; Clinical Relevance
Language	English
Publishing date	2022-12-16
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-022-03513-7
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Article ; Online: The impact of the approval of prothrombin complex concentrates for vitamin K antagonist-related intracerebral hemorrhage: A retrospective study.

Watanabe, Sadayoshi / Matsumoto, Shoji / Nakahara, Ichiro / Morioka, Jun / Hasebe, Akiko / Tanabe, Jun / Suyama, Kenichiro / Ishihara, Takuma / Ohta, Tsuyoshi / Hatano, Taketo / Nagata, Izumi / Hirose, Yuichi

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

2022 Volume 31, Issue 12, Page(s) 106861

Abstract: ... concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage.: Materials and ... methods: We retrospectively studied all patients with vitamin K antagonist-related ... in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage ...

Abstract	Objectives: This study aimed to determine the impact of the approval of prothrombin complex concentrates on the treatment of vitamin K antagonist-related intracerebral hemorrhage. Materials and methods: We retrospectively studied all patients with vitamin K antagonist-related intracerebral hemorrhage treated with prothrombin complex concentrate at our institutes between January 2010 and June 2021. Before approval, prothrombin complex concentrate was administered as either 500 or 1000 IU at the physician's discretion (previous dose group). After approval, we adopted the manufacturer's recommended regimen (recommended dose group). The primary outcome was post-administration international normalized ratio. Secondary outcomes were the amount of prothrombin complex concentrate administered and proportion of post-administration international normalized ratio <1.5, hematoma expansion, thrombotic events within 30 days, modified Rankin scale 0-3 at discharge, and in-hospital mortality. Results: Thirty-two and 19 patients in the previous and recommended dose groups, respectively, were included. The post-administration international normalized ratio significantly differed between groups. The prothrombin complex concentrate dose and proportion of patients achieving post-administration international normalized ratio <1.5 were significantly higher in the recommended dose group than in the previous dose group (1500 IU vs. 500 IU, p<0.001 and 100% vs. 68%, p = 0.008). The proportions of hematoma expansion, thromboembolic events, modified Rankin scale 0-3, and mortality did not differ between groups. Conclusion: After prothrombin complex concentrate approval, prothrombin time-international normalized ratio correction was more effective with a significant increase in the prothrombin complex concentrates dose for vitamin K antagonist-associated intracerebral hemorrhage; however, there was no apparent difference in clinical outcomes.
MeSH term(s)	Humans ; Retrospective Studies ; Vitamin K ; Prothrombin/therapeutic use ; Blood Coagulation Factors/adverse effects ; Anticoagulants/adverse effects ; International Normalized Ratio ; Cerebral Hemorrhage/chemically induced ; Cerebral Hemorrhage/drug therapy ; Hematoma/drug therapy ; Fibrinolytic Agents/therapeutic use
Chemical Substances	prothrombin complex concentrates (37224-63-8) ; Vitamin K (12001-79-5) ; Prothrombin (9001-26-7) ; Blood Coagulation Factors ; Anticoagulants ; Fibrinolytic Agents
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1131675-5
ISSN	1532-8511 ; 1052-3057
ISSN (online)	1532-8511
ISSN	1052-3057
DOI	10.1016/j.jstrokecerebrovasdis.2022.106861
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Article ; Online: Relationship between K-line distance and surgical outcome in cases of laminoplasty for cervical ossification of the posterior longitudinal ligament.

Miyazaki, Masashi / Ishihara, Toshinobu / Kanezaki, Shozo / Hirakawa, Masashi / Iwasaki, Tatsuya / Abe, Tetsutaro / Tsumura, Hiroshi

Medicine

2022 Volume 101, Issue 47, Page(s) e31605

Abstract: ... of the posterior longitudinal ligament (OPLL), the relationship between the surgical outcomes, the distance between the kyphosis-line (K ... women) with cervical OPLL who underwent laminoplasty. "K-line distance" was measured as the minimum ... interval between the K-line and OPLL on lateral radiographs. The following factors were analyzed: K-line ...

Abstract	Although previous studies indicate that changes in cervical alignment after laminoplasty and dynamic factors influence surgical outcomes of cervical ossification of the posterior longitudinal ligament (OPLL), the relationship between the surgical outcomes, the distance between the kyphosis-line (K-line) and OPLL, and dynamic factors have not yet been quantitatively evaluated. The purpose of the present study was to analyze the relationship between ΔK-line distance and surgical outcomes in cases of laminoplasty for OPLL of the cervical spine. We retrospectively reviewed 46 consecutive patients (33 men and 13 women) with cervical OPLL who underwent laminoplasty. "K-line distance" was measured as the minimum interval between the K-line and OPLL on lateral radiographs. The following factors were analyzed: K-line distance in neutral, flexion, and extension neck positions, ΔK-line distance, preoperative C2-7 range of motion (ROM), preoperative segmental ROM, preoperative C2-7 lordotic angle, occupying ratio of the OPLL, disease duration, preoperative and postoperative Japanese Orthopaedic Association (JOA) score, and recovery rate. Patients were divided into flexion K-line (+) and flexion K-line (-) groups. We then analyzed the influence of the K-line distance on surgical outcomes and conducted multivariate analysis to analyze the factors affecting surgical outcomes. The JOA score recovery rate in the flexion K-line (-) group was significantly lower than that in the flexion K-line (+) group (P = .024). The ΔK-line distance was significantly negatively correlated with the JOA score recovery rate (r = -0.531, P < .001). Additionally, multivariate analysis showed that ΔK-line distance (OR = -2.143, P = .015) was negatively correlated with the JOA score recovery rate. The ΔK-line distance is considered useful for the quantitative evaluation of dynamic factors and static compression factors due to OPLL through the measurement of dynamic radiographic images.
MeSH term(s)	Male ; Humans ; Female ; Laminoplasty ; Longitudinal Ligaments ; Osteogenesis ; Retrospective Studies ; Ossification of Posterior Longitudinal Ligament/diagnostic imaging ; Ossification of Posterior Longitudinal Ligament/surgery ; Kyphosis ; Musculoskeletal Abnormalities ; Cervical Vertebrae/diagnostic imaging ; Cervical Vertebrae/surgery ; Treatment Outcome
Language	English
Publishing date	2022-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000031605
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Article ; Online: Endogenous human retrovirus-K is not increased in the affected tissues of Japanese ALS patients.

Ishihara, Tomohiko / Koyama, Akihide / Hatano, Yuya / Takeuchi, Ryoko / Koike, Yuka / Kato, Taisuke / Tada, Mari / Kakita, Akiyoshi / Onodera, Osamu

Neuroscience research

2022 Volume 178, Page(s) 78–82

Abstract: Activation of human endogenous retrovirus-K (HERV-K) is one of the proposed risk factors ... for amyotrophic lateral sclerosis (ALS). The HERV-K envelope protein has been reported to show neurotoxicity, and development ... failed to show HERV-K activation in ALS. In this study, we analyzed the expression of HERV-K mRNA ...

Abstract	Activation of human endogenous retrovirus-K (HERV-K) is one of the proposed risk factors for amyotrophic lateral sclerosis (ALS). The HERV-K envelope protein has been reported to show neurotoxicity, and development of therapy with reverse transcriptase inhibitors is being investigated. On the other hand, some reports have failed to show HERV-K activation in ALS. In this study, we analyzed the expression of HERV-K mRNA in the motor cortex and spinal cord of 15 Japanese patients with sporadic ALS and 19 controls using reverse transcriptase droplet digital PCR. This revealed no significant increase of HERV-K expression in ALS-affected tissues, suggesting that the association between ALS and HERV-K remains questionable.
MeSH term(s)	Amyotrophic Lateral Sclerosis/genetics ; Endogenous Retroviruses/genetics ; Humans ; Japan ; Motor Cortex ; RNA, Messenger
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2022-02-02
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605842-5
ISSN	1872-8111 ; 0168-0102 ; 0921-8696
ISSN (online)	1872-8111
ISSN	0168-0102 ; 0921-8696
DOI	10.1016/j.neures.2022.01.009
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Article ; Online: Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression.

Lotinun, Sutada / Ishihara, Yoshihito / Nagano, Kenichi / Kiviranta, Riku / Carpentier, Vincent T / Neff, Lynn / Parkman, Virginia / Ide, Noriko / Hu, Dorothy / Dann, Pamela / Brooks, Daniel / Bouxsein, Mary L / Wysolmerski, John / Gori, Francesca / Baron, Roland

The Journal of clinical investigation

2019 Volume 129, Issue 8, Page(s) 3058–3071

Abstract: ... for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion ...

Abstract	Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion in osteocytes prevented the increase in osteocyte lacunar area seen during lactation, as well as the effects of lactation to increase osteoclast numbers and decrease trabecular bone volume, cortical thickness and mechanical properties. In addition, Ctsk deletion in osteocytes increased bone Parathyroid Hormone related Peptide (PTHrP), prevented the decrease in serum Parathyroid Hormone (PTH) induced by lactation, but amplified the increase in serum 1,25(OH)2D. The net result of these changes is to maintain serum and milk calcium levels in the normal range, ensuring normal offspring skeletal development. Our studies confirm the fundamental role of osteocytic perilacunar remodeling in physiological states of lactation and provides genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25-Dyhydroxyvitamin D (1,25(OH)2D), osteoclastogenesis and bone loss in response to the high calcium demand associated with lactation.
MeSH term(s)	Animals ; Bone Remodeling/physiology ; Bone Resorption/etiology ; Bone Resorption/prevention & control ; Calcium/analysis ; Cathepsin K/deficiency ; Cathepsin K/physiology ; Cells, Cultured ; Female ; Lactation/physiology ; Mice ; Mice, Inbred C57BL ; Osteocytes/physiology ; Osteogenesis ; Osteoporosis/etiology ; Osteoporosis/prevention & control ; Parathyroid Hormone/blood
Chemical Substances	Parathyroid Hormone ; Cathepsin K (EC 3.4.22.38) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI122936
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Article ; Online: Erratum: Azimuthal Anisotropy of K_{S}^{0} and Λ+Λ[over ¯] Production at Midrapidity from Au+Au Collisions at sqrt[s]_{NN}=130 GeV [Phys. Rev. Lett. 89, 132301 (2002)].

Adler, C / Ahammed, Z / Allgower, C / Amonett, J / Anderson, B D / Anderson, M / Averichev, G S / Balewski, J / Barannikova, O / Barnby, L S / Baudot, J / Bekele, S / Belaga, V V / Bellwied, R / Berger, J / Bichsel, H / Billmeier, A / Bland, L C / Blyth, C O /

Bonner, B E / Boucham, A / Brandin, A / Bravar, A / Cadman, R V / Caines, H / Calderón de la Barca Sánchez, M / Cardenas, A / Carroll, J / Castillo, J / Castro, M / Cebra, D / Chaloupka, P / Chattopadhyay, S / Chen, Y / Chernenko, S P / Cherney, M / Chikanian, A / Choi, B / Christie, W / Coffin, J P / Cormier, T M / Cramer, J G / Crawford, H J / Csanád, M / Deng, W S / Derevschikov, A A / Didenko, L / Dietel, T / Draper, J E / Dunin, V B / Dunlop, J C / Eckardt, V / Efimov, L G / Emelianov, V / Engelage, J / Eppley, G / Erazmus, B / Fachini, P / Faine, V / Filimonov, K / Finch, E / Fisyak, Y / Flierl, D / Foley, K J / Fu, J / Gagliardi, C A / Gagunashvili, N / Gans, J / Gaudichet, L / Germain, M / Geurts, F / Ghazikhanian, V / Grachov, O / Grigoriev, V / Guedon, M / Gushin, E / Hallman, T J / Hardtke, D / Harris, J W / Henry, T W / Heppelmann, S / Herston, T / Hippolyte, B / Hirsch, A / Hjort, E / Hoffmann, G W / Horsley, M / Huang, H Z / Humanic, T J / Igo, G / Ishihara, A / Ivanshin, Yu I / Jacobs, P / Jacobs, W W / Janik, M / Johnson, I / Jones, P G / Judd, E G / Kaneta, M / Kaplan, M / Keane, D / Kiryluk, J / Kisiel, A / Klay, J / Klein, S R / Klyachko, A / Konstantinov, A S / Kopytine, M / Kotchenda, L / Kovalenko, A D / Kramer, M / Kravtsov, P / Krueger, K / Kuhn, C / Kulikov, A I / Kunde, G J / Kunz, C L / Kutuev, R Kh / Kuznetsov, A A / Lakehal-Ayat, L / Lamont, M A C / Landgraf, J M / Lange, S / Lansdell, C P / Lasiuk, B / Laue, F / Lebedev, A / Lednický, R / Leontiev, V M / LeVine, M J / Li, Q / Lindenbaum, S J / Lisa, M A / Liu, F / Liu, L / Liu, Z / Liu, Q J / Ljubicic, T / Llope, W J / LoCurto, G / Long, H / Longacre, R S / Lopez-Noriega, M / Love, W A / Ludlam, T / Lynn, D / Ma, J / Ma, R / Majka, R / Margetis, S / Markert, C / Martin, L / Marx, J / Matis, H S / Matulenko, Yu A / McShane, T S / Meissner, F / Melnick, Yu / Meschanin, A / Messer, M / Miller, M L / Milosevich, Z / Minaev, N G / Mitchell, J / Moiseenko, V A / Moore, C F / Morozov, V / de Moura, M M / Munhoz, M G / Nelson, J M / Nevski, P / Niida, T / Nikitin, V A / Nogach, L V / Norman, B / Nurushev, S B / Odyniec, G / Ogawa, A / Okorokov, V / Oldenburg, M / Olson, D / Paic, G / Pandey, S U / Panebratsev, Y / Panitkin, S Y / Pavlinov, A I / Pawlak, T / Perevoztchikov, V / Peryt, W / Petrov, V A / Planinic, M / Pluta, J / Porile, N / Porter, J / Poskanzer, A M / Potrebenikova, E / Prindle, D / Pruneau, C / Putschke, J / Rai, G / Rakness, G / Ravel, O / Ray, R L / Razin, S V / Reichhold, D / Reid, J G / Retiere, F / Ridiger, A / Ritter, H G / Roberts, J B / Rogachevski, O V / Romero, J L / Rose, A / Roy, C / Rykov, V / Sakrejda, I / Salur, S / Sandweiss, J / Saulys, A C / Savin, I / Schambach, J / Scharenberg, R P / Schmitz, N / Schroeder, L S / Schüttauf, A / Schweda, K / Seger, J / Seliverstov, D / Seyboth, P / Shahaliev, E / Shestermanov, K E / Shimanskii, S S / Shvetcov, V S / Skoro, G / Smirnov, N / Snellings, R / Sorensen, P / Sowinski, J / Spinka, H M / Srivastava, B / Stephenson, E J / Stock, R / Stolpovsky, A / Strikhanov, M / Stringfellow, B / Struck, C / Suaide, A A P / Sugarbaker, E / Suire, C / Šumbera, M / Surrow, B / Symons, T J M / Szanto de Toledo, A / Szarwas, P / Tai, A / Takahashi, J / Tang, A H / Thomas, J H / Thompson, M / Tikhomirov, V / Todoroki, T / Tokarev, M / Tonjes, M B / Trainor, T A / Trentalange, S / Tribble, R E / Trofimov, V / Tsai, O / Ullrich, T / Underwood, D G / Van Buren, G / VanderMolen, A M / Vasilevski, I M / Vasiliev, A N / Vigdor, S E / Voloshin, S A / Wang, F / Ward, H / Watson, J W / Wells, R / Westfall, G D / Whitten, C / Wieman, H / Willson, R / Wissink, S W / Witt, R / Wood, J / Xu, N / Xu, Z / Yakutin, A E / Yamamoto, E / Yang, J / Yepes, P / Yurevich, V I / Zanevski, Y V / Zborovský, I / Zhang, H / Zhang, W M / Zoulkarneev, R / Zubarev, A N

Physical review letters

2021 Volume 127, Issue 8, Page(s) 89901

Abstract: This corrects the article DOI: 10.1103/PhysRevLett.89.132301. ...

Abstract	This corrects the article DOI: 10.1103/PhysRevLett.89.132301.
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Published Erratum
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.127.089901
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Article ; Online: Clinical Concentrations of Local Anesthetics Bupivacaine and Lidocaine Differentially Inhibit Human Kir2.x Inward Rectifier K+ Channels.

Nakahira, Kei / Oshita, Kensuke / Itoh, Masayuki / Takano, Makoto / Sakaguchi, Yoshiro / Ishihara, Keiko

Anesthesia and analgesia

2016 Volume 122, Issue 4, Page(s) 1038–1047

Abstract: Background: Inward rectifier K channels of the Kir2.x subfamily are widely expressed in neuronal ...

Abstract	Background: Inward rectifier K channels of the Kir2.x subfamily are widely expressed in neuronal tissues, controlling neuronal excitability. Previous studies reported that local anesthetics (LAs) do not affect Kir2 channels. However, the effects have not been studied at large concentrations used in regional anesthesia. Methods: This study used the patch-clamp technique to examine the effects of bupivacaine and lidocaine on Kir2.1, Kir2.2, and Kir2.3 channels expressed in human embryonic kidney 293 cells. Results: When applied extracellularly in whole-cell recordings, both LAs inhibited Kir2.x currents in a voltage-independent manner. Inhibition with bupivacaine was slow and irreversible, whereas that with lidocaine was fast and reversible. Kir2.3 displayed a greater sensitivity to bupivacaine than Kir2.1 and Kir2.2 (50% inhibitory concentrations at approximately 5 minutes, 0.6 vs 8-10 mM), whereas their sensitivities to lidocaine were similar (50% inhibitory concentrations, 1.5-2.7 mM). Increases in the charged/neutral ratio of the LAs at an acidic extracellular pH attenuated their inhibitory effects, and a permanently charged lidocaine derivative QX-314 exhibited no effects when applied extracellularly. Inside-out experiments demonstrated that inhibition of Kir2.1 with cytoplasmic lidocaine and QX-314 was rapid and reversible, whereas that induced by bupivacaine was slow and irreversible. Furthermore, dose-inhibition relations for the charged form of bupivacaine and lidocaine obtained at different cytoplasmic pHs could be approximated by a single relation for each LA. Conclusions: The results indicate that both LAs at clinical concentrations equilibrated rapidly with the intracellular milieu, differentially inhibiting Kir2.x channel function from the cytoplasmic side.
MeSH term(s)	Anesthetics, Local/metabolism ; Anesthetics, Local/pharmacology ; Bupivacaine/metabolism ; Bupivacaine/pharmacology ; Cytoplasm/drug effects ; Cytoplasm/metabolism ; HEK293 Cells ; Humans ; Lidocaine/metabolism ; Lidocaine/pharmacology ; Potassium Channels, Inwardly Rectifying/antagonists & inhibitors
Chemical Substances	Anesthetics, Local ; KCNJ2 protein, human ; KCNJ4 protein, human ; Kir2.2 channel ; Potassium Channels, Inwardly Rectifying ; Lidocaine (98PI200987) ; Bupivacaine (Y8335394RO)
Language	English
Publishing date	2016-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80032-6
ISSN	1526-7598 ; 0003-2999
ISSN (online)	1526-7598
ISSN	0003-2999
DOI	10.1213/ANE.0000000000001137
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Article: Search for the Decay K L0-->pi0nu nu[over].

Ahn, J K / Akune, Y / Baranov, V / Chen, K F / Comfort, J / Doroshenko, M / Fujioka, Y / Hsiung, Y B / Inagaki, T / Ishibashi, S / Ishihara, N / Ishii, H / Iwai, E / Iwata, T / Kato, I / Kobayashi, S / Komatsubara, T K / Kurilin, A S / Kuzmin, E /

Lednev, A / Lee, H S / Lee, S Y / Lim, G Y / Ma, J / Matsumura, T / Moisseenko, A / Morii, H / Morimoto, T / Nakano, T / Nanjo, H / Nix, J / Nomura, T / Nomachi, M / Okuno, H / Omata, K / Perdue, G N / Podolsky, S / Sakashita, K / Sasaki, T / Sasao, N / Sato, H / Sato, T / Sekimoto, M / Shinkawa, T / Sugaya, Y / Sugiyama, A / Sumida, T / Suzuki, S / Tajima, Y / Takita, S / Tsamalaidze, Z / Tsukamoto, T / Tung, Y C / Wah, Y W / Watanabe, H / Wu, M L / Yamaga, M / Yamanaka, T / Yoshida, H Y / Yoshimura, Y

Physical review letters

2008 Volume 100, Issue 20, Page(s) 201802

Abstract: We performed a search for the K L0-->pi0nu nu[over] decay at the KEK 12-GeV proton synchrotron. No ...

Abstract	We performed a search for the K L0-->pi0nu nu[over] decay at the KEK 12-GeV proton synchrotron. No candidate events were observed. An upper limit on the branching ratio for the decay was set to be 6.7 x 10(-8) at the 90% confidence level.
Language	English
Publishing date	2008-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.100.201802
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Article: Species differences between human and rat in the substrate specificity of cathepsin K.

Tada, Sachiyo / Tsutsumi, Kae / Ishihara, Hideki / Suzuki, Kenji / Gohda, Keigo / Teno, Naoki

Journal of biochemistry

2008 Volume 144, Issue 4, Page(s) 499–506

Abstract: Cathepsin K is known to play an important role in bone resorption, and it has the P2 specificity ... for proline. Rat cathepsin K has 88% identity with the human enzyme. However, it has been reported ... that its enzymatic activity for a Cbz-Leu-Arg-MCA substrate is lower than that of human cathepsin K, and that the rat enzyme ...

Abstract	Cathepsin K is known to play an important role in bone resorption, and it has the P2 specificity for proline. Rat cathepsin K has 88% identity with the human enzyme. However, it has been reported that its enzymatic activity for a Cbz-Leu-Arg-MCA substrate is lower than that of human cathepsin K, and that the rat enzyme is not well inhibited by human cathepsin K inhibitors. For this study, we prepared recombinant enzyme to investigate the substrate specificity of rat cathepsin K. Cleavage experiments using the fragment of type I collagen and peptidic libraries demonstrated that rat cathepsin K preferentially hydrolyses the substrates at the P2 Hyp position. Comparison of the S2 site between rat and human cathepsin K sequences indicated that two S2 residues at Ser134 and Val160 in rat are varied to Ala and Leu, respectively, in the human enzyme. Cleavage experiments using two single mutants, S134A and V160L, and one double mutant, S134A/V160L, of rat cathepsin K showed that all the rat mutants lost the P2 Hyp specificity. The information obtained from our comparative studies on rat and human cathepsin K should make a significant impact on developing specific inhibitors of human cathepsin K since rat is usually used as test species.
MeSH term(s)	Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Base Sequence ; Catalytic Domain/genetics ; Cathepsin K ; Cathepsins/chemistry ; Cathepsins/genetics ; Cathepsins/metabolism ; Collagen Type I/genetics ; Collagen Type I/metabolism ; Crystallography, X-Ray ; DNA Primers/genetics ; Dipeptides/metabolism ; Humans ; In Vitro Techniques ; Kinetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Peptide Fragments/genetics ; Peptide Fragments/metabolism ; Rats ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Species Specificity ; Substrate Specificity
Chemical Substances	Collagen Type I ; DNA Primers ; Dipeptides ; Peptide Fragments ; Recombinant Proteins ; Cathepsins (EC 3.4.-) ; CTSK protein, human (EC 3.4.22.38) ; Cathepsin K (EC 3.4.22.38) ; Ctsk protein, rat (EC 3.4.22.38)
Language	English
Publishing date	2008-10
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvn093
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