Functions and mechanisms of ascorbic acid in maintaining hepatic cytochrome P-450

• Project/Area Number: 25660102
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Food science
• Research Institution: Nagoya University
• Principal Investigator: Horio Fumihiko 名古屋大学, 生命農学研究科, 教授 (20165591)
• Co-Investigator(Renkei-kenkyūsha): Murai Atsushi 名古屋大学, 大学院生命農学研究科, 准教授 (10313975) ; Kobayashi Misato 名古屋大学, 大学院生命農学研究科, 助教 (20456586)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アスコルビン酸 / アスコルビン酸欠乏 / シトクロムP-450 / ヘム分解 / ヘムオキシゲナーゼ / ビタミンC / Heme oxygenase-1

Outline of Final Research Achievements

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. Firstly, ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Nextly, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

Research Products

• [Journal Article] ビタミンCの生合成制御と生体防御・疾患に関わる生理機能の解析 (2015)
  • Author(s): 堀尾文彦
  • Journal Title: ビタミン Volume: 89 Pages: 528-536
  • NAID: 110010006367
  • Peer Reviewed
• [Journal Article] Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats. (2014)
  • Author(s): Kobayashi, M., Hoshinaga, Y., Miura, N., Tokuda, Y., Shigeoka, S., Murai, A. and Horio, F.
  • Journal Title: Biosci.Biotechnol.Biochem. Volume: 78 Pages: 1060-1066
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] アスコルビン酸のLPS誘発性炎症での救命作用の機構解析 (2016)
  • Author(s): 辻野祥伍、川出野絵、徳田優希、小林美里、松田幹、村井篤嗣、堀尾文彦
  • Organizer: 日本農芸化学会2016年度大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-28
• [Presentation] アスコルビン酸欠乏時の肝臓STAT3の活性化と炎症変化 (2015)
  • Author(s): 川出野絵、辻野祥伍、徳田優希、小林美里、村井篤嗣、堀尾文彦
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-06-06
• [Presentation] アスコルビン酸摂取のLPS誘発性TNFα産生に対する抑制作用 (2015)
  • Author(s): 辻野祥伍、川出野絵、徳田優希、小林美里、村井篤嗣、堀尾文彦
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-06-06
• [Presentation] ビタミンCの生合成制御と生体防御・疾患に関わる生理機能の解析 (2015)
  • Author(s): 堀尾文彦
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-06-05
  • Invited
• [Presentation] アスコルビン酸欠乏時の肝臓でのIL-6、IL-1シグナル系因子の発現上昇と炎症用変化 (2014)
  • Author(s): 川出野絵、徳田優希、辻野祥伍、村井篤嗣、小林美里、堀尾文彦
  • Organizer: 日本ビタミン学会第66回大会
  • Place of Presentation: 姫路
  • Year and Date: 2014-06-14
• [Presentation] アスコルビン酸欠乏による肝臓の転写因子STAT3の活性化とその制御下遺伝子の発現解析 (2014)
  • Author(s): 川出野絵、徳田優希、辻野祥伍、小林美里、村井篤嗣、重岡 成、堀尾文彦
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 江別
  • Year and Date: 2014-05-31
• [Presentation] アスコルビン酸欠乏における肝蔵の酸化ストレス防御系と炎症関連因子の経時的発現解析
  • Author(s): 徳田優希、川出野絵、村井篤嗣、小林美里、堀尾文彦
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋
• [Presentation] ODSラットのアスコルビン酸欠乏初期における肝蔵の酸化ストレス状態とその防御系の変動
  • Author(s): 徳田優希、川出野絵、小林美里、村井篤嗣、後藤 廉、吉村和也、堀尾文彦
  • Organizer: 日本ビタミン学会第65回大会
  • Place of Presentation: 東京