Antioxidative effect of ascorbate peroxidase derived from Cyanidioschyzon merolae in mammalian cells

• Project/Area Number: 17K11648
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Hitomi Suzuro 九州歯科大学, 歯学部, 講師 (70548924)
• Co-Investigator(Kenkyū-buntansha): 小野 堅太郎 九州歯科大学, 歯学部, 教授 (40316154) ; 古株 彰一郎 九州歯科大学, 歯学部, 教授 (30448899) ; 松本 謙一郎 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, グループリーダー(定常) (10297046)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ascorbate peroxidase / Cyanidioschyzon merolae / oxidative stress / reactive oxygen species / アスコルビン酸ペルオキシダーゼ / シゾン / 抗酸化作用 / 潰瘍性口内炎 / 口腔生理学

Outline of Final Research Achievements

Ascorbate peroxidase (APX) derived from Cyanidioschyzon merolae, which is a primitive red alga living in high-temperature and acidic environment, has been reported greater anti-oxidative capacity than those in other plants. In the present study, we examined a possibility to increase anti-oxidative capacity in mammalian cells by the expression of Cyanidioschyzon merolae-drived APX (cAPX). cAPX gene was introduced into the mice fibroblast-like cell line C3H10T1/2. Production of reactive oxygen species (ROS) and/or cell viability after heat, H2O2 and acid stimulations were assessed. Heat and H2O2 stimulations caused ROS production. cAPX-expressed cells were more tolerant to oxidative stress induced by heat, H2O2 and acid stimulations than control cells. From these results, introduction of cAPX increases antioxidative capacity in mammalian cells.

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、動物細胞におけるAPXの機能解明に役立つだけではなく、がん治療を原因として局所に産生される過剰な活性酸素種（ROS）の除去に応用できる可能性がある。がんの放射線治療や化学療法では、がん細胞に対する ROSの傷害作用を抑制することなく、がん細胞以外の“局所”でROSを調節することが望ましい。今後、cAPX発現細胞を用いた細胞シートなどによる粘膜保護が可能になれば、粘膜細胞が酸化ストレスに強い抵抗性を獲得し、酸化ストレスを原因とした粘膜潰瘍や疼痛の抑制に役立つ可能性がある。

Research Products

• [Journal Article] Endothelin-1 Elicits TRP-Mediated Pain in an Acid-Induced Oral Ulcer Model (2018)
  • Author(s): Nodai T.、Hitomi S.、Ono K.、Masaki C.、Harano N.、Morii A.、Sago-Ito M.、Ujihara I.、Hibino T.、Terawaki K.、Omiya Y.、Hosokawa R.、Inenaga K.
  • Journal Title: Journal of Dental Research Volume: 印刷中 Issue: 8 Pages: 901-908
  • DOI: 10.1177/0022034518762381
  • Peer Reviewed / Open Access
• [Presentation] Functional expression of ascorbate peroxidase derived from Cyanidioschyzon merolae in mammalian cells (2020)
  • Author(s): Suzuro Hitomi, Shoichiro Kokabu, Kenichiro Matsumoto, Izumi Ujihara, Kentaro Ono
  • Organizer: 第97回日本生理学会大会
• [Presentation] Cisplatin-induced intraoral neuropathy due to TRPA1 sensitization in rats. (2019)
  • Author(s): Hitomi，S.，Yamaguchi，K.，Seta，Y.，Ujihara，I.，Ono，K.
  • Organizer: 9th FAOPS Congress
  • Int'l Joint Research
• [Presentation] 抗がん薬による唾液分泌機能低下は口内炎治癒を妨げる (2018)
  • Author(s): 1.人見涼露, 氏原泉, 左合ー伊藤美紗, 鹿山武海, 小野堅太郎
  • Organizer: 第95回日本生理学会大会
• [Presentation] Gingerol and shogaol, the herbal contents, relief oral ulcerative mucositis-induced pain through sodium channel blockage. (2017)
  • Author(s): 11.Hitomi, S., Ono, K., Ujihara, I., Terawaki, K., Matsumoto, C., Omiya, Y., Inenaga, K
  • Organizer: The 3rd Oral neuroscience
  • Int'l Joint Research
• [Presentation] Oral ulcerative mucositis induces pain via endothelin receptors. (2017)
  • Author(s): 15.Nodai, T., Hitomi, S., Masaki, C., Ito, M., Hosokawa, R., Ono, K. and Inenaga, K
  • Organizer: The 5th Asia-Pacific Conference
  • Int'l Joint Research