Analysis of intestinal cholesterol absorption for the personalized medicine against hypercholesterolemia

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790152
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: WATANABE Hiroshi Kumamoto University, 薬学部, 講師 (70398220)
• Project Period (FY): 2009 – 2010
• Keywords: コレステロール / トランスポータ / 代謝酵素 / 体内動態 / 腎不全

Research Abstract

We show that, when parental Chinese hamster ovary (CHO) cells are briefly exposed to ^3H-cholesteryl linoleate (CL) labeled-LDL, newly liberated ^3H-LDL-CHOL appears in membranes rich in trans-Golgi network (TGN) long before it becomes available for re-esterification at the endoplasmic reticulum (ER) or for efflux at the plasma membrane. In mutant cells lacking NPC1, the appearance of newly liberated ^3H-LDL-CHOL in the TGN-rich fractions is much reduced. We demonstrate that knockdown by RNAi of 3 TGN-specific SNAREs (VAMP4, syntaxin 6, and syntaxin 16) reduces >/=50% of the LDL-CHOL transport in intact cells and in vitro.

Research Products

• [Journal Article] Structural insights into differences in drug binding selectivity between two forms of human {alpha}1-acid glycoprotein genetic variants, the A and F1*S forms. (2011)
  • Author(s): Nishi K, Ono T, Nakamura T, Fukunaga N, Izumi M, Watanabe H, Suenaga A, Maruyama T, Yamagata Y, Curry S, Otagiri M.
  • Journal Title: J Biol Chem. in press
  • Peer Reviewed
• [Journal Article] Organic anion transporters play an important role in the uptake of p-cresyl sulfate, a uremic toxin, in the kidney. (2011)
  • Author(s): Miyamoto Y, Watanabe H, Noguchi T, Kotani S, Nakajima M, Kadowaki D, Otagiri M, Maruyama T.
  • Journal Title: Nephrol Dial Transplant. in press
  • Peer Reviewed
• [Journal Article] Fluid Resuscitation with Hemoglobin Vesicles Prevents Escherichia coli Growth via Complement Activation in a Hemorrhagic Shock Rat Model. (2011)
  • Author(s): Taguchi K, Ogaki S, Watanabe H, Kadowaki D, Sakai H, Kobayashi K, Horinouchi H, Maruyama T, Otagiri M.
  • Journal Title: J Pharmacol Exp Ther. 337 Pages: 201-208
  • Peer Reviewed
• [Journal Article] Vitamin d receptor activator reduces oxidative stress in hemodialysis patients with secondary hyperparathyroidism. (2011)
  • Author(s): Tanaka M, Tokunaga K, Komaba H, Itoh K, Matsushita K, Watanabe H, Kadowaki D, Maruyama T, Otagiri M, Fukagawa M.
  • Journal Title: Ther Apher Dial. 15 Pages: 161-168
  • Peer Reviewed
• [Journal Article] New insight into the redox properties of uremic solute indoxyl sulfate as a pro- and anti-oxidant. (2011)
  • Author(s): Miyamoto Y, Watanabe H, Otagiri M, Maruyama T.
  • Journal Title: Ther Apher Dial. 15 Pages: 129-131
  • Peer Reviewed
• [Journal Article] Repeated injection of high doses of hemoglobin-encapsulated liposomes (hemoglobin vesicles) induces accelerated blood clearance in a hemorrhagic shock rat model. (2011)
  • Author(s): Taguchi K, Iwao Y, Watanabe H, Kadowaki D, Sakai H, Kobayashi K, Horinouchi H, Maruyama T, Otagiri M.
  • Journal Title: Drug Metab Dispos. 39 Pages: 484-489
  • Peer Reviewed
• [Journal Article] Alteration in the pharmacokinetics of hemoglobin-vesicles in a rat model of chronic liver cirrhosis is associated with Kupffer cell phagocyte activity. (2011)
  • Author(s): Taguchi K, Miyasato M, Watanabe H, Sakai H, Tsuchida E, Horinouchi H, Kobayashi K, Maruyama T, Otagiri M.
  • Journal Title: J Pharm Sci. 100 Pages: 775-783
  • Peer Reviewed
• [Journal Article] Superior plasma retention of a cross-linked human serum albumin dimer in nephrotic rats as a new type of plasma expander. (2010)
  • Author(s): Taguchi K, Urata Y, Anraku M, Watanabe H, Kawai K, Komatsu T, Tsuchida E, Maruyama T, Otagiri M.
  • Journal Title: Drug Metab Dispos. 38 Pages: 2124-2129
  • Peer Reviewed
• [Journal Article] Hepatically-metabolized and -excreted artificial oxygen carrier, hemoglobin vesicles, can be safely used under conditions of hepatic impairment. (2010)
  • Author(s): Taguchi K, Miyasato M, Ujihira H, Watanabe H, Kadowaki D, Sakai H, Tsuchida E, Horinouchi H, Kobayashi K, Maruyama T, Otagiri M.
  • Journal Title: Toxicol Appl Pharmacol. 248 Pages: 234-241
  • Peer Reviewed
• [Journal Article] Albumin fusion of thioredoxin-the production and evaluation of its biological activity for potential therapeutic applications. (2010)
  • Author(s): Ikuta S, Chuang VT, Ishima Y, Nakajou K, Furukawa M, Watanabe H, Maruyama T, Otagiri M.
  • Journal Title: J Control Release. 147 Pages: 17-23
  • Peer Reviewed
• [Journal Article] The uremic solute indoxyl sulfate acts as an antioxidant against superoxide anion radicals under normal-physiological conditions. (2010)
  • Author(s): Miyamoto Y, Iwao Y, Tasaki Y, Sato K, Ishima Y, Watanabe H, Kadowaki D, Maruyama T, Otagiri M.
  • Journal Title: FEBS Lett. 584 Pages: 2816-2820
  • Peer Reviewed
• [Journal Article] Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics. (2010)
  • Author(s): Hirata K, Maruyama T, Watanabe H, Maeda H, Nakajou K, Iwao Y, Ishima Y, Katsumi H, Hashida M, Otagiri M.
  • Journal Title: J Control Release. 145 Pages: 9-16
  • Peer Reviewed
• [Presentation] 尿毒症物質CMPFの酸化ストレス誘発メカニズム (2011)
  • Author(s): 宮本洋平、岩尾康範、米良克美、渡邊博志、門脇大介、異島優、佐藤圭創、小田切優樹、丸山徹
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡
  • Year and Date: 20110328-20110331
• [Presentation] 一酸化炭素結合型赤血球による肝CYP保護効果 (2011)
  • Author(s): 大柿滋、田口和明、渡邊博志、門脇大介、小田切優樹、丸山徹
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡,グランシップ
  • Year and Date: 20110328-20110331
• [Presentation] ブレオマイシン誘発肺線維症に対するアルブミン-チオレドキシン融合体の有用性評価 (2011)
  • Author(s): 田中遼大, 古川真斗, 異島優, 田中健一郎, 水島徹, 渡邊博志, 小田切優樹, 丸山徹
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡, グランシップ
  • Year and Date: 20110328-20110331
• [Presentation] 尿毒症物質p-cresyl sulfateの酸化ストレスに及ぼす影響 (2011)
  • Author(s): 本田大輔、宮本洋平、渡邊博志、門脇大介、丸山徹、小田切優樹
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: ツインメッセ静岡
  • Year and Date: 20110328-20110331
• [Presentation] MS解析を用いた慢性肝炎時におけるヒト血清アルブミンのレドックス解析と構造及び機能との関連性 (2011)
  • Author(s): 南雲恒平, 杉森剛志, 窪田和幸, 山田尚之, 異島優, 渡邊博志, 田中基彦, 佐々木裕, 小田切優樹, 丸山徹
  • Organizer: 日本薬学会大131年会
  • Place of Presentation: 静岡, グランシップ
  • Year and Date: 20110321-20110323
• [Presentation] 肝疾患時におけるアルブミンの構造及び機能評価 (2010)
  • Author(s): 南雲恒平, 杉森剛志, 田中基彦, 佐々木裕, 異島優, 渡邊博志, 窪田和幸, 山田尚之, 小田切優樹, 丸山徹
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学薬学部
  • Year and Date: 20101211-20101212
• [Presentation] BLM誘発肺線維症に対するアルブミン-チオレドキシン融合タンパク質の有用性評価 (2010)
  • Author(s): 田中遼大, 古川真斗, 異島優, 田中健一郎, 水島徹, 渡邊博志, 小田切優樹, 丸山徹
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学薬学部
  • Year and Date: 20101211-20101212
• [Presentation] 一酸化炭素を付加した赤血球は大量出血時における肝チトクロームP450を保護する (2010)
  • Author(s): 大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
  • Organizer: 第27回日本薬学会九州支部大会
  • Place of Presentation: 長崎大学薬学部
  • Year and Date: 20101211-20101212
• [Presentation] 尿毒症物質CMPFの生体内レドックス特性 (2010)
  • Author(s): 宮本洋平、岩尾康範、渡邊博志、門脇大介、佐藤圭創、小田切優樹、丸山徹
  • Organizer: 第27回臨床フリーラジカル会議
  • Place of Presentation: 京都, 烟川
  • Year and Date: 20101203-20101204
• [Presentation] 出血性ショックモデルラットにおける一酸化炭素結合型赤血球の肝チトクロームP450保護効果 (2010)
  • Author(s): 大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
  • Organizer: 第32回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 富山国際会議場
  • Year and Date: 20101129-20101130
• [Presentation] 1-acid glycoprotein enhances the expression of hemoglobin scavenge receptor CD163 through the activation of TLR4 signaling (2010)
  • Author(s): Komori H, Watanabe H, Syuto T, Maruyama T, Otagiri M
  • Organizer: 第4回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 東京大学武田先端知ビル
  • Year and Date: 20101127-20101128
• [Presentation] Involvement of hemoglobin・chain on plasma membrane in uptake of human・1-acid glycoprotein into liver (2010)
  • Author(s): Komori H, Uehara N, Nishi K, Watanabe H, Maruyama T, Otagiri M
  • Organizer: The Pharmaceutical Sciences World Congress 2010
  • Place of Presentation: Morial Convention Center, New Orleans,USA
  • Year and Date: 20101114-20101118
• [Presentation] 出血性ショックモデルラットにおける一酸化炭素結合型赤血球のチトクロームP450の保護効果 (2010)
  • Author(s): 大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
  • Organizer: 第17回日本血液代替物学会
  • Place of Presentation: 熊本国際交流会館
  • Year and Date: 20101018-20101019
• [Presentation] CHARACTERIZATION OF STRUCTURE AND FUNCTION OF HUMAN SERUM ALBUMIN IN PATIENTS WITH LIVER DISEASE (2010)
  • Author(s): Kohei Nagumo, Tsuyoshi Sugimori, Motohiko Tanaka, Yutaka Sasaki, Yu Ishima, Hiroshi Watanabe, Kazuyuki Kubota, Naoyuki Yamada, Masaki Otagiri, Toru Maruyama.
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 20101007-20101009
• [Presentation] IMPROVED THERAPEUTIC EFFECT OF THIOREDOXIN BY FUSION TO HUMAN SERUM ALBUMIN AGAINST BLEOMYCIN-INDUCED PULMONARY FIBROSIS (2010)
  • Author(s): 田中遼大, 古川真斗, 異島優, 田中健一郎, 水島徹, 渡邊博志, 小田切優樹, 丸山徹
  • Organizer: 日本薬物動態学会第25回年会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 20101007-20101009
• [Presentation] 1-酸性糖タンパク質によるCD163の発現誘導 (2010)
  • Author(s): Komori H, Watanabe H, Syuto T,Maruyama T, Otagiri M
  • Organizer: 第35回西日本薬剤学研究会
  • Place of Presentation: 大分, 九重共同研修所
  • Year and Date: 20100917-20100918
• [Presentation] Hepatic uptake of・1-acid glycoprotein through hemoglobin・-chain-mediated endocytic pathway (2010)
  • Author(s): Komori H, Uehara N, Nishi K, Watanabe H, Maruyama T, Otagiri M
  • Organizer: 9^<th> International ISSX meeting
  • Place of Presentation: Istanbul Lutfi Kirdar Convention and Exhibition Center-Harbiye, Istanbul, Turkey
  • Year and Date: 20100904-20100908
• [Presentation] 丸山徹尿毒症物質CMPFの酸化ストレス誘発機序解明 (2010)
  • Author(s): 宮本洋平、岩尾康範、渡邊博志、門脇大介、佐藤圭創、小田切優樹
  • Organizer: 第25回日本薬剤学会
  • Place of Presentation: あわぎんホール徳島県郷土文化会館
  • Year and Date: 20100511-20100514
• [Presentation] 一酸化炭素結合型赤血球による肝チトクロームP450の保護効果 (2010)
  • Author(s): 大柿滋、田口和明、渡邊博志、小田切優樹、丸山徹
  • Organizer: 第25回日本薬剤学会
  • Place of Presentation: あわぎんホール徳島県郷土文化会館
  • Year and Date: 20100511-20100514
• [Remarks] ホームページ等
  • URL: http://www.pharm.kumamoto-u.ac.jp/Labs/Yakuzai/