Analysis of the defensive roles of isoform amino acid repair enzyme on protein damage by oxidative stress

• Project/Area Number: 26461194
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Iwate Medical University
• Principal Investigator: Yamauchi Kohei 岩手医科大学, 医学部, 教授 (20200579)
• Co-Investigator(Kenkyū-buntansha): 小笠原 正人 岩手医科大学, 医学部, 准教授 (00325367)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 異性体アミノ酸 / PCMT1 / COPD / 酸化ストレス / Prohibitin 1 / ミトコンドリア / オートファジー / Prohibitin1 / オートファジ― / D-体アスパラギン酸残基 / PCMT / 異性体化

Outline of Final Research Achievements

The isomerization of aspartic acid and asparagine residues among several post-translational protein modifications is one of the damages by oxidative stress which occurs in the pathogenesis of chronic obstructive pulmonary disease (COPD). Its D-isoaspartyl (D-isoAsp) and D-aspartic acid (D-Asp) cause the protein structure alteration and functional impairment. This process is partially reversed by the protein carboxyl-isoaspartyl methyltransferase 1 (PCMT1) repair enzyme. We investigated PCMT1 expression in the pulmonary tissue from COPD patients and evaluated its significant reduction. The mitochondrial protein, Prohibitin1 (PHB1) is deeply associated with production of active oxygen species and oxidative stress. Under low PCMT1 condition、D-Asp content in PHB1 increased significantly. In this regard, deamidation of Asp residues in the mitochondrial protein, PHB1 is associated with aging via changes of cellular organelles.

Research Products

• [Journal Article] The protective role of protein L-isoaspartyl (D-aspartate) O-methyltransferase for maintenance of mitochondrial morphology in A549 cell. (2016)
  • Author(s): Ogasawara M, Otani M, Takano M, Shudou M, Inaba Y, Nirasawa S, Takahashi S, Kiyoi T, Tanaka Y, Kameda K, Kunugita N, Maeyama K, Sano K, Yamashita M, Yamauchi K.
  • Journal Title: Exp Lung Res Volume: 42 Issue: 5 Pages: 245-62
  • DOI: 10.1080/01902148.2016.1197984
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Therapeutic implication of genetic variants of IL13 and STAT4 in airway remodelling with bronchial asthma. (2016)
  • Author(s): Nakamura Y, Suzuki R, Mizuno T, Abe K, Chiba S, Horii Y, Tsuboi J, Ito S, Obara W, Tanita T, Kanno H, Yamauchi K.
  • Journal Title: Clin Exp Allergy Volume: 46 Issue: 9 Pages: 1152-1161
  • DOI: 10.1111/cea.12710
  • Peer Reviewed
• [Journal Article] A phosphatidylinositol 3-kinase inhibitor strongly suppressed pulmonary vascular remodeling of allergic vasculitis in a murine model (2016)
  • Author(s): Oikawa Y, Sasaki N, Niisato M, Nakamura Y, Yamauchi K
  • Journal Title: Exp Lung Res Volume: 17 Issue: 3 Pages: 1-10
  • DOI: 10.3109/01902148.2016.1157226
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of a single-codon E746 deletion in exon 19 of the epidermal growth factor receptor. (2016)
  • Author(s): Ogasawara M, Nakamura Y, Morikawa N, Nitanai H, Moriguchi S, Chiba R, Saito H, Ohta M, Tanita T, Sugai T, Maeyama K, Yamauchi K, Takaoka Y.
  • Journal Title: Cancer Chemother Pharmacol Volume: 77(5) Issue: 5 Pages: 1019-1029
  • DOI: 10.1007/s00280-016-3021-y
  • Peer Reviewed / Open Access
• [Journal Article] Chaperone protein l-isoaspartate (d-aspartyl) O-methyltransferase as a novel predictor of poor prognosis in lung adenocarcinoma. (2016)
  • Author(s): Saito H, Yamashita M, Ogasawara M, Yamada N, Niisato M, Tomoyasu M, Deguchi H, Tanita T, Ishida K, Sugai T, Yamauchi K.
  • Journal Title: Hum Pathol Volume: 50 Pages: 1-10
  • DOI: 10.1016/j.humpath.2015.11.006
  • Peer Reviewed / Open Access
• [Journal Article] Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin. (2016)
  • Author(s): 119.Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K.
  • Journal Title: Pulm Pharmacol Ther. Volume: 38 Pages: 27-35
  • DOI: 10.1016/j.pupt.2016.04.003
  • Peer Reviewed
• [Journal Article] Development of Lymphatic Capillary Network Along the Alveolar Walls of Autopsied Human Lungs with Pneumonia. (2016)
  • Author(s): 120.Yamashita M, Niisato M, Hanasaka T, Iwama N, Takahashi T, Sugai T, Ono M, Yamauchi K.
  • Journal Title: Lymphat Res Biol. Volume: 14 Issue: 4 Pages: 210-9
  • DOI: 10.1089/lrb.2015.0042
  • Peer Reviewed
• [Journal Article] Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin (2016)
  • Author(s): Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K
  • Journal Title: Pulmonary Pharmacology and Therapeutics Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Detection of cerebral microvascular lesions using 7 T MRI in patients with neuropsychiatric systemic lupus erythematosus (2015)
  • Author(s): 12. Murata O, Sasaki N, Sasaki M, Kowada K, Ninomiya Y, Oikawa Y, Kobayashi H, Nakamura Y, Yamauchi K
  • Journal Title: Neuroreport Volume: 26 Issue: 1 Pages: 27-32
  • DOI: 10.1097/wnr.0000000000000297
  • Peer Reviewed
• [Journal Article] Periostin in the bronchial lavage fluid of asthma patients (2015)
  • Author(s): akamura, Y., Nagashima, H., Ohta, S., Ono, J., Yamauchi, K. & Izuhara, K.
  • Journal Title: Allergology International Volume: 64 Issue: 2 Pages: 209-210
  • DOI: 10.1016/j.alit.2015.01.001
  • NAID: 130005290284
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lymphangiogenic factors are associated with the severity of hypersensitivity pneumonitis (2015)
  • Author(s): Yamashita M, Mouri T, Niisato M, Nitanai H, Kobayashi H, Ogasawara M, Endo R, Konishi K, Sugai T, Sawai T, Yamauchi K
  • Journal Title: BMJ Open Respir Res Volume: 29 Issue: 1 Pages: e000085-e000085
  • DOI: 10.1136/bmjresp-2015-000085
  • Peer Reviewed / Open Access
• [Journal Article] Rapamycin Attenuates Pulmonary Allergic Vasculitis in Murine Model by Reducing TGF-β Production in the Lung (2014)
  • Author(s): Koizumi R, Sasaki N, Nakamura Y, Suzuki N, Sawai T, Yamauchi K
  • Journal Title: Allergology International Volume: 63 Issue: 3 Pages: 457-466
  • DOI: 10.2332/allergolint.13-OA-0679
  • NAID: 130004687704
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Presentation] 小胞体ストレスに対するProtein-L-isoaspartate (D-aspartate) O-methyltransfearse (PIMT) 代償発現の不足は肺腺癌浸潤を促す (2017)
  • Author(s): 山下雅大、小笠原正人、斎藤平佐、山内広平
  • Organizer: 第５７回呼吸器学会学術講演会
  • Place of Presentation: 東京
• [Presentation] A phosphatidylinositol 3-kinase inhibitor strongly suppressed pulmonary vascular remodeling of allergic vasculitis in a murine model (2015)
  • Author(s): Oikawa Y, Sasaki N, Niisato M, Nakamura Y, Yamauchi K.
  • Organizer: Annual Congress of the European Respiratory Society
  • Place of Presentation: Amsterdam
  • Year and Date: 2015-09-28
  • Int'l Joint Research
• [Presentation] Mitigation of tight junction protein dysfunction in lung microvascular endothelial cells with pitavastatin (2015)
  • Author(s): Suzuki R, Nakamura Y, Chiba S, Mizuno T, Abe K, Horii Y, Nagashima H, Tanita T, Yamauchi K
  • Organizer: Annual Congress of the European Respiratory Society
  • Place of Presentation: Amsterdam
  • Year and Date: 2015-09-27
  • Int'l Joint Research
• [Presentation] Analysis of The Pulmonary Functions of The Residents In Sanriku Seacoast After The Tsunami Disaster In The East Japan Great Earthquake. (2014)
  • Author(s): Hiromi Nagashima et al.
  • Organizer: American Thoracic Society;International Conference
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2014-05-17 – 2014-05-21
• [Presentation] 岩手県における東日本大震災被災者の肺機能障害の解析 (2014)
  • Author(s): 長島広相他、８名
  • Organizer: 第111回日本内科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-25 – 2014-04-27