A new approach for the treatment of cerebrovascular diseases based on the regulation of nerve growth factor in glial cells

• Project/Area Number: 23592081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Hirosaki University
• Principal Investigator: YOSHIDA Hidemi 弘前大学, 医学(系)研究科(研究院), 講師 (40201008)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脳血管障害 / アストロサイト / NGF / エダラボン / カルノシン酸 / ニューロン / アミロイドβ / セクレターゼ / グリア / アルツハイマー病 / 脳血管障害学 / 脳保護 / 神経変性疾患 / 神経毒性

Research Abstract

The present study revealed that edaravone (a brain-penetrant free radical scavenger used for the patients with the acute phase of stroke) and carnosic acid (CA), a phenolic diterpene compound found in the labiate herbs rosemary and sage, synergistically enhances the expression of nerve growth factor (NGF) in cultured human astrocytes under not only normoxia but also hypoxia or reoxygenation.
Also, we found that CA suppresses the production of amyloid-beta peptides (Abeta, a group of dementia-causing molecules) 1-42 (and also Abeta 1-43 in astrocytes) in cultured SH-SY5Y human neuroblastoma cells and human U373MG astrocytoma cells. The inhibitory effect of CA was effective in astrocytes even under hypoxia/reoxygenation.
These results may be simultaneously connected with development of the both methods for the amelioration of postischemic neuronal dysfunction in cerebrovascular diseases and the prevention of Abeta-mediated diseases, particularly Alzheimer's disease.

Research Products

• [Journal Article] Carnosic acid suppresses the production of amyloid-beta 1-42 and 1-43 by inducing an alpha-secretase TACE/ADAM17 in U373MG human astrocytoma cells. (2014)
  • Author(s): Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K, Itoh K, Takahashi I, Imaizumi T
  • Journal Title: Neurosci Res Volume: 79 Pages: 89-94
  • DOI: 10.1016/j.neures.2013.11.004
  • Peer Reviewed
• [Journal Article] ISG54 and ISG56 are induced by TLR3 signaling in U373MG human astrocytoma cells: Possible involvement in CXCL10 expression. (2014)
  • Author(s): Imaizumi T, Numata A, Yano C, Yoshida H, Meng P, Hayakari R, Xing F, Wang L, Matsumiya T, Tanji K, Tatsuta T, Murakami M, Tanaka H.
  • Journal Title: Neurosci Res Volume: 000 Pages: 34-42
  • DOI: 10.1016/j.neures.2014.03.001
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-αsynergistically enhances polyinosinic-polycytidylic acid-induced toll-like receptor 3 signaling in cultured normal human mesangial cells : possible involvement in the pathogenesis of lupus nephritis (2014)
  • Author(s): Imaizumi T, Aizawa T, Hayakari R, Xing F, Meng P, Tsuruga K, Matsumiya T, Yoshida H, Wang L, Tatsuta T, Tanaka H
  • Journal Title: Clin Exp Nephrol Volume: 14
  • Peer Reviewed
• [Journal Article] Role of type I- and type II-interferon in expression of melanoma differentiation-associated gene-5 in HSC-3 oral squamous carcinoma cells (2014)
  • Author(s): Matsumiya T, Hayakari R, Narita N, Ito R, Kon T, Kubota K, Sakaki H, Yoshida H, Imaizumi T, Kobayashi W, Kimura H
  • Journal Title: Biomed Res Volume: 35(1) Pages: 9-16
  • NAID: 130004903864
  • URL: https://www.jstage.jst.go.jp/article/biomedres/35/1/35_9/_article
• [Journal Article] Mizoribine selectively attenuates monocyte chemoattractant protein-1 production in cultured human glomerular mesangial cell: a possible benefit of its use in the treatment of lupus nephritis. (2014)
  • Author(s): Aizawa T, Imaizumi T, Tsuruga K, Watanabe S, Chiba Y, Matsumiya T, Yoshida H, Tanaka H.
  • Journal Title: Nephrology (Carlton) Volume: 19 Issue: 1 Pages: 47-52
  • DOI: 10.1111/nep.12171
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-α synergistically enhances polyinosinic-polycytidylic acid-induced toll-like receptor 3 signaling in cultured normal human mesangial cells: possible involvement in the pathogenesis of lupus nephritis. (2014)
  • Author(s): Imaizumi T, Aizawa T, Hayakari R, Xing F, Meng P, Tsuruga K, Matsumiya T, Yoshida H, Wang L, Tatsuta T, Tanaka H.
  • Journal Title: Clin Exp Nephrol Volume: 000
  • Peer Reviewed
• [Journal Article] Role of type I- and type II-interferon in expression of melanoma differentiation-associated gene-5 in HSC-3 oral squamous carcinoma cells. (2014)
  • Author(s): Matsumiya T, Hayakari R, Narita N, Ito R, Kon T, Kubota K, Sakaki H, Yoshida H, Imaizumi T, Kobayashi W, Kimura H.
  • Journal Title: Biomed Res Volume: 35 Pages: 9-16
  • NAID: 130004903864
  • Peer Reviewed
• [Journal Article] Glomerular expression of myxovirus resistance protein 1 in human mesangial cells: possible activation of innate immunity in the pathogenesis of lupus nephritis. (2013)
  • Author(s): Watanabe S, Imaizumi T, Tsuruga K, Aizawa T, Ito T, Matsumiya T, Yoshida H, Joh K, Ito E, Tanaka H.
  • Journal Title: Nephrology (Carlton) Volume: 18 Issue: 12 Pages: 833-837
  • DOI: 10.1111/nep.12155
  • Peer Reviewed
• [Journal Article] Urinary fractalkine and monocyte chemoattractant protein-1 as possible predictors of disease activity of childhood glomerulonephritis (2013)
  • Author(s): Aizawa T, Imaizumi T, Tsuruga K, Watanabe S, Yoshida H, Kumagai N, Ito E, Tanaka H
  • Journal Title: Tohoku J Exp Med Volume: 231(4) Pages: 265-270
  • NAID: 130004822389
  • URL: https://www.jstage.jst.go.jp/article/tjem/231/4/231_265/_article.
• [Journal Article] Novel role for molecular transporter importin 9 in posttranscriptional regulation of IFN-ε expression. (2013)
  • Author(s): Matsumiya T, Xing F, Ebina M, Hayakari R, Imaizumi T, Yoshida H, Kikuchi H, Topham MK, Satoh K, Stafforini DM.
  • Journal Title: J Immunol Volume: 191 Issue: 4 Pages: 1907-15
  • DOI: 10.4049/jimmunol.1201925
  • Peer Reviewed
• [Journal Article] MDA5 and ISG56 mediate CXCL10 expression induced by toll-like receptor 4 activation in U373MG human astrocytoma cells. (2013)
  • Author(s): Imaizumi T, Murakami K, Ohta K, Seki H, Matsumiya T, Meng P, Hayakari R, Xing F, Aizawa-Yashiro T, Tatsuta T, Yoshida H, Kijima H.
  • Journal Title: Neurosci Res. Volume: 76 Issue: 4 Pages: 195-206
  • DOI: 10.1016/j.neures.2013.05.002
  • Peer Reviewed
• [Journal Article] TLR4 signaling induces retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5 in mesangial cells. (2013)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Watanabe S, Matsumiya T, Yoshida H, Tatsuta T, Xing F, Meng P, Hayakari R, Tsuruga K, Tanaka H.
  • Journal Title: J Nephrol Volume: 26 Issue: 5 Pages: 886-893
  • DOI: 10.5301/jn.5000254
  • Peer Reviewed
• [Journal Article] Interaction between interferon-stimulated gene 56 and melanoma differentiation-associated gene 5 in toll-like receptor 3 signaling in normal human mesangial cells (2013)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Matsumiya T, Yoshida H, Watanabe S, Tsuruga K, Tatsuta T, Xing F, Hayakari R, Meng P, Tanaka H.
  • Journal Title: Am J Nephrol Volume: 37 Issue: 2 Pages: 118-125
  • DOI: 10.1159/000346415
  • Peer Reviewed
• [Journal Article] Carnosic acid suppresses the production of amyloid-β 1-42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells (2013)
  • Author(s): Meng P, Yoshida H, Matsumiya T, Imaizumi T, Tanji K, Xing F, Hayakari R, Dempoya J, Tatsuta T, Aizawa-Yashiro T, Mimura J, Kosaka K, Itoh K, Satoh K
  • Journal Title: Neurosci Res Volume: 75 Issue: 2 Pages: 4-102
  • DOI: 10.1016/j.neures.2012.11.007
  • Peer Reviewed
• [Journal Article] Glomerular expression of fractalkine is induced by polyinosinic-polycytidylic acid in human mesangial cells: possible involvement of fractalkine after viral infection (2013)
  • Author(s): Aizawa-Yashiro T, Imaizumi T, Tsuruga K, Watanabe S, Matsumiya T, Hayakari R, Yoshida H, Satoh K, Ito E, Tanaka H.
  • Journal Title: Pediatr Res Volume: 73 Issue: 2 Pages: 180-186
  • DOI: 10.1038/pr.2012.165
  • Peer Reviewed
• [Journal Article] Effects of Brazilian green propolis on double-stranded RNA-mediated induction of interferon-inducible gene and inhibition of recruitment of polymorphonuclear cells (2013)
  • Author(s): Hayakari R, Matsumiya T, Xing F, Tayone JC, Dempoya J, Tatsuta T, Aizawa-Yashiro T, Imaizumi T, Yoshida H, Satoh K
  • Journal Title: J Sci Food Agric Volume: 93(3) Issue: 3 Pages: 646-651
  • DOI: 10.1002/jsfa.5892
• [Journal Article] Urinary fractalkine and monocyte chemoattractant protein-1 as possible predictors of disease activity of childhood glomerulonephritis. (2013)
  • Author(s): Aizawa T, Imaizumi T, Tsuruga K, Watanabe S, Yoshida H, Kumagai N, Ito E, Tanaka H.
  • Journal Title: Tohoku J Exp Med. 2013;231(4):265-70. Volume: 231 Pages: 265-270
  • NAID: 130004822389
  • Peer Reviewed
• [Journal Article] Foreign RNA induces the degradation of mitochondrial antiviral signaling protein (MAVS)the role of intracellular antiviral factors. (2012)
  • Author(s): Xing F, Matsumiya T, Onomoto K, Hayakari R, Imaizumi T, Yoshida H, Yoneyama M, Fijita T, Satoh K
  • Journal Title: PLoS One Volume: 7(9) Issue: 9 Pages: e45136-e45136
  • DOI: 10.1371/journal.pone.0045136
  • Peer Reviewed
• [Journal Article] Double-stranded RNA induces biphasic STAT1 phosphorylation by both type I IFN-dependent and type I IFN-independent pathways (2012)
  • Author(s): Dempoya J, Matsumiya T, Imaizumi T, Hayakari R, Xing F, Yoshida H, Okumura K, Satoh K
  • Journal Title: J Virol Volume: 86(23) Issue: 23 Pages: 12760-12769
  • DOI: 10.1128/jvi.01881-12
  • Peer Reviewed
• [Journal Article] Melanoma differentiation-associated gene 5 regulates the expression of a chemokine CXCL10 in human mesangial cells : implications for chronic inflammatory renal diseases (2012)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Tsuruga K, Tanaka H, Matsumiya T, Yoshida H, Tatsuta T, Xing F, Hayakari R, Satoh K
  • Journal Title: Tohoku J Exp Med Volume: 228(1) Pages: 17-26
  • NAID: 10031025369
  • URL: https://www.jstage.jst.go.jp/article/tjem/228/1/228_17/_article.
  • Peer Reviewed
• [Journal Article] Fukuda S : Expression of melanoma differentiation associated gene 5 (MDA5) is increased in human gastric mucosa infected with Helicobacter pyroli (2012)
  • Author(s): Tatsuta T, Imaizumi T, Shimoyama T,Sawaya M, Tanji K, Matsumiya T, Yoshida H, Satoh K
  • Journal Title: J Clin Pathol Volume: 65 Issue: 9 Pages: 839-843
  • DOI: 10.1136/jclinpath-2011-200590
  • Peer Reviewed
• [Journal Article] Melanoma differentiation-associated gene 5 regulates the expression of a chemokine CXCL10 in human mesangial cells: implications for chronic inflammatory renal diseases (2012)
  • Author(s): Imaizumi T, Aizawa-Yashiro T, Tsuruga K, Tanaka H, Matsumiya T, Yoshida H, Tatsuta T, Xing F, Hayakari R, Satoh K
  • Journal Title: Tohoku J Exp Med Volume: 228 Pages: 17-26
  • NAID: 10031025369
  • Peer Reviewed
• [Journal Article] Edaravone and carnosic acid synergistically enhance the expression of nerve growth factor in human astrocytes under hypoxia/reoxygenation (2011)
  • Author(s): Yoshida H, Mimura J, Imaizumi T, Matsumiya T, Ishikawa A, Metoki N, Tanji K, Ota K, Hayakari R, Kosaka K, Itoh K, Satoh K
  • Journal Title: Neurosci Res Volume: 69 Issue: 4 Pages: 291-298
  • DOI: 10.1016/j.neures.2010.12.016
  • Peer Reviewed
• [Journal Article] Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes (2011)
  • Author(s): Mimura J, Kosaka K, Maruyama A, Satoh T, Harada N, Yoshida H, Satoh K, Yamamoto M, Itoh K
  • Journal Title: J Biochem Volume: 150 Issue: 2 Pages: 209-217
  • DOI: 10.1093/jb/mvr065
  • NAID: 10030587033
  • Peer Reviewed
• [Journal Article] Imbalance towards Th1 pathway predominance in purpura neohritis with proteinuria. (2011)
  • Author(s): Tsuruga K, Watanabe S, Oki E, Aizawa-Yashiro T, Yoshida H, Imaizumi T, Ito E, Tanaka H
  • Journal Title: Pediat Nephrol Volume: 26 Issue: 12 Pages: 2253-2258
  • DOI: 10.1007/s00467-011-1996-5
  • Peer Reviewed
• [Journal Article] Polyinosinic-polycytidylic acid induces the expression of interferon-stimulated gene 20 in mesangial cells (2011)
  • Author(s): Imaizumi T, Tanaka H, Mechti N, Matsumiya T, Yoshida H, Sato F, Aizawa-Yashiro T, Tsuruga K, Hayakari R, Satoh K
  • Journal Title: Nephron Exp Nephrol Volume: 119(2) Issue: 2 Pages: e40-e48
  • DOI: 10.1159/000328923
  • Peer Reviewed
• [Journal Article] Basic-helix-loop-helix transcription factor DEC2 constitutes negative feedback loop in IFN-g-mediated inflammatory responses in human mesangial cells. (2011)
  • Author(s): Imaizumi T, Yoshida T, Sato F, Tanaka H, Yashiro-Aizawa K, Hayakari R, Kijima H, Matsumiya T, Tsuruga H, Satoh K
  • Journal Title: Immunol Lett Volume: 136 Issue: 1 Pages: 37-43
  • DOI: 10.1016/j.imlet.2010.11.009
  • Peer Reviewed
• [Presentation] カルノシン酸はアミロイドβによる神経系細胞のアポトーシス経路活性化を抑制する (2014)
  • Author(s): 孟鵬飛、吉田秀見、丹治邦和、松宮朋穂、邢飛、早狩亮、三村純正、伊東健、今泉忠淳
  • Organizer: 第151回弘前医学会例会
  • Place of Presentation: 弘前大学医学部コミュニケーションセンター(青森県弘前市)
  • Year and Date: 2014-01-31
• [Presentation] カルノシン酸はアミロイドβによる神経系細胞のアポトーシス経路活性化を抑制する (2014)
  • Author(s): 孟鵬飛、吉田秀見、丹治邦和、松宮朋穂、シン・フェイ、早狩亮、三村純正、伊東健、今泉忠淳
  • Organizer: 第151回弘前医学会例会
  • Place of Presentation: 弘前大学医学部コミュニケーションセンター（青森県）
• [Presentation] カルノシン酸は培養ヒト神経芽腫細胞のアミロイドβ(1-42)分泌を抑制する (2013)
  • Author(s): 孟鵬飛、吉田秀見、松宮朋穂、今泉忠淳、丹治邦和、邢飛、早狩亮、三村純正、伊東健
  • Organizer: 第150回弘前医学会例会
  • Place of Presentation: 弘前大学医学部コミュニケーションセンター(青森県弘前市)
  • Year and Date: 2013-01-25
• [Presentation] カルノシン酸は培養ヒト神経芽腫細胞のアミロイドβ（1-42）分泌を抑制する
  • Author(s): 孟鵬飛、吉田秀見、松宮朋穂、今泉忠淳、丹治邦和、シン飛、早狩亮、三村純正、伊東健、佐藤敬
  • Organizer: 第150回弘前医学会例会
  • Place of Presentation: 弘前大学医学部コミュニケーションセンター（青森県）
• [Remarks]
  • URL: http://vascularbiology.web.fc2.com
• [Remarks] 弘前大学大学院医学研究科脳血管病態学公式ブログ
  • URL: http://vascularbiology.blog.fc2.com/blog-category-6.html
• [Remarks] 弘前大学大学院医学研究科脳血管病態学公式ブログ
  • URL: http://vascularbiology.blog.fc2.com/blog-category-6.html