2010 Fiscal Year Final Research Report
Metabolism of amyloid proteins and methods for detecting amyloid proteins
| Project/Area Number |
21790541
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
UEDA Mitsuharu Kumamoto University, 大学院・生命科学研究部, 助教 (60452885)
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| Project Period (FY) |
2009 – 2010
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| Keywords | アミロイドーシス / 血清蛋白質 / 質量分析 |
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| Research Abstract |
Systemic AA amyloidosis is one of the most severe complications of chronic inflammatory disorders, particularly rheumatoid arthritis. It is well known that, similar to an infectious prion protein, amyloid-enhancing factor (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits AA amyloidosis in vivo remained to be fully elucidated. In the present study, we focused on finding cell-free forms of AEF and its carriers in circulation by using the murine transfer model of AA amyloidosis. We first determined that circulating cell-free AEF existed in blood and plasma in mice with systemic AA amyloidosis. Second, we established that plasma exosomes containing AA amyloid oligomers derived from serum amyloid A had AEF activity and could transmit systemic AA amyloidosis via a prion-like mechanism. These novel findings should provide insights into the transmission mechanism of systemic amyloidoses.
We previously reported that two cases of aged vervet monkeys (Cercopithecus
… More
aethiops) spontaneously developed TTR amyloidosis and showed clinical symptoms mimicking human TTR amyloidosis. However, the pathogenesis of TTR amyloidosis in vervet monkeys and relationship to the human disease remained to be elucidated. The aims of the present study were to elucidate the pathogenesis of TTR amyloidosis in the vervet monkeys, and to verify pathological relationship to the human TTR amyloidosis. First, using over 120 tissue specimens of various primates and clinical cardiac findings of vervet monkeys and crab-eating macaques, we showed that aged vervet monkeys developed TTR amyloidosis mainly causing cardiac dysfunction by means of physicochemical examinations, but other non-human primates showed neither TTR amyloid deposits nor cardiac dysfunctions. Next, we determined that vervet monkeys had the species-specific TTR allele. Taken together, we propose that the aged vervet monkeys mimic the human TTR amyloidosis and the monkey is a precious species as an animal model for this hereditary disease of human. Less
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[Journal Article] Loss of functional albumin triggers acceleration of transthyretin amyloid fibril formation in familial amyloidotic polyneuropathy.2011
Author(s)
Kugimiya T, Jono H, Saito S, Maruyama T, Kadowaki D, Misumi Y, Hoshii Y, Tasaki M, Su Y, Ueda M, Obayashi K, Shono M, Otagiri M, Ando Y.
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Journal Title
Peer Reviewed
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[Journal Article] Amyloid neuropathy in a younger domino liver-transplanted recipient.2011
Author(s)
Obayashi K, Yamashita T, Tasaki M, Ueda M, Shono M, Jono H, Ohshima T, Ohya Y, Asonuma K, Inomata Y, Ando Y.
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Journal Title
Muscle Nerve 43
Pages: 449-450
Peer Reviewed
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[Journal Article] Hepatic stellate cells accelerate the malignant behavior of cholangiocarcinoma cells.2011
Author(s)
Okabe H, Beppu T, Hayashi H, Ishiko T, Masuda T, Otao R, Hasita H, Jono H, Ueda M, Shinriki S, Ando Y, Baba H.
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Journal Title
Ann Surg Oncol 18
Pages: 1175-1184
Peer Reviewed
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[Journal Article] Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation.2010
Author(s)
Koike H, Kiuchi T, Iijima M, Ueda M, Ando Y, Morozumi S, Tomita M, Kawagashira Y, Watanabe H, Katsuno M, Shimoyama Y, Okazaki Y, Kamei H, Sobue G.
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Journal Title
J Neurol Neurosurg Psychiatry (Epub ahead of print)
Peer Reviewed
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[Journal Article] Transmission of circulating cell-free AA amyloid oligomers in exosomes vectors via a prion-like mechanism.2010
Author(s)
Tasaki M, Ueda M, Ochiai S, Tanabe Y, Murata S, Misumi Y, Su Y, Sun X, Shinriki S, Jono H, Shono M, Obayashi K, Ando Y.
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Journal Title
Biochem Res Commun 400(contributedequally)
Pages: 559-562
Peer Reviewed
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[Journal Article] Multicenter evaluation of prototype real-time PCR assays for Epstein-Barr virus and cytomegalovirus DNA in whole blood samples from transplant recipients.2010
Author(s)
Ito Y, Takakura S, Ichiyama S, Ueda M, Ando Y, Matsuda K, Hidaka E, Nakatani K, Nishioka J, Nobori T, Kajiyama N, Kimura H.
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Journal Title
Microbiol Immunol. 54
Pages: 516-522
Peer Reviewed
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[Journal Article] Midkine expression is correlated with an adverse prognosis and is down-regulated by p53 in oral squamous cell carcinoma.2010
Author(s)
Ota K, Fujimori H, Ueda M, Jono H, Shinriki S, Ota T, Sueyoshi T, Taura M, Taguma A, Kai H, Shinohara M, Ando Y.
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Journal Title
Int J Oncol 37
Pages: 797-804
Peer Reviewed
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[Journal Article] Aberrant expression of serum amyloid A in head and neck squamous cell carcinoma.2010
Author(s)
Shinriki S, Ueda M, Ota K, Nakamura M, Kudo M, Ibusuki M, Kim J, Yoshitake Y, Fukuma D, Jono H, Kuratsu J, Shinohara M, Ando Y.
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Journal Title
Journal of Oral Pathology and Medicine 39
Pages: 41-47
Peer Reviewed
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[Journal Article] Distinct characteristics of amyloid deposits in early- and late-onset transthyretin Val30Met familial amyloid polyneuropathy.2009
Author(s)
Koike H, Ando Y, Ueda M, Kawagashira Y, Iijima M, Fujitake J, Hayashi M, Yamamoto M, Mukai E, Nakamura T, Katsuno M, Hattori N, Sobue G.
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Journal Title
J Neurol Sci 287
Pages: 178-184
Peer Reviewed
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[Journal Article] Humanized Anti-Interleukin-6 Receptor Antibody Suppresses Tumor Angiogenesis and In Vivo Growth of Human Oral Squamous Cell Carcinoma.2009
Author(s)
Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, Oike Y, Endo M, Ibusuki M, Hiraki A, Nakayama H, Yoshitake Y, Shinohara M, Ando Y.
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Journal Title
Clin Cancer Res 15
Pages: 5426-5434
Peer Reviewed
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[Journal Article] Midkine in plasma as a novel breast cancer marker.2009
Author(s)
Ibusuki M, Fujimori H, Yamamoto Y, Ota K, Ueda M, Shinriki S, Taketomi M, Sakuma S, Shinohara M, Iwase H, Ando Y.
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Journal Title
Cancer Sci 100
Pages: 1735-1739
Peer Reviewed
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[Journal Article] SELDI-TOF MS evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy.2009
Author(s)
Ueda M, Misumi Y, Mizuguchi M, Nakamura M, Yamashita T, Sekijima Y, Ota K, Shinriki S, Jono H, Ikeda SI, Suhr OB, Ando Y.
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Journal Title
Clin Chem 55
Pages: 1223-1227
Peer Reviewed
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[Journal Article] Antitumor effect of humanized anti-IL-6 receptor antibody (tocilizumab) on glioma cell proliferation.2009
Author(s)
Kudo M, Jono H, Shinriki S, Yano S, Nakamura H, Makino K, Hide T, Muta D, Ueda M, Ota K, Ando Y, Kuratsu J.
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Journal Title
J Neurosurg 111
Pages: 219-225
Peer Reviewed
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[Presentation] Analyses of vervet monkeys suffering from ATTR amyloidosis : A candidate model animal for human TTR-related amyloidosis.2010
Author(s)
Ueda M, Ageyama N, Nakamura S, Chambers J, Misumi Y, Nakaguma R, Shinriki S, Shono M, Jono H, Obayashi K, Une Y, Ando Y.
Organizer
XII International Symposium on Amyloidosis.
Place of Presentation
Rome.Crowne Plaza Rome-St.Peter`s Rome, Italy
Year and Date
20100418-20100421
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[Remarks] ホームページ等
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