Inducer of heme oxygenase-1 cobalt protoporphyrin accelerates autophagy and suppresses oxidative damages during lipopolysaccharide treatment in rat liver

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: UNUMA Kana 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (30586425)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: autophagy / endotoxemia / heme oxygenase-1 / lipopolysaccharide

Research Abstract

A large reduction in liver mitochondrial protein and induction of autophagy were observed in LPS-treated rats.Electron microscopic and immunohistochemical analyses demonstrated autophagic vacuoles in LPS-treated rat liver. Oxidative stress markers were increased in LPS-treated animals; CoPP treatment ablated these alterations. An inhibitor for the opening of mitochondrial permeability transition pore, cyclosporine A, suppressed oxidative stress as well as liver damage during LPS administration. CoPP promoted auto- phagy and prevented rats from liver damage during LPS administration.HO-1 promotes autophagy and elimination of damaged mitochondria thereby repressing oxidative stress in LPS-treated rat liver, revealing a novel mechanism for protec- tion by HO-1 against septic liver damage.

Research Products

• [Journal Article] I n d u c e r o f h e me o x y g e n a s e - 1 c o b a l t p r o t o p o r p h y r i n a c c e l e r a t e s a u t o p h a g y a n d s u p p r e s s e s o x i d a t i v e d a ma g e s d u r i n g l i p o p o l y s a c c h a r i d e t r e a t me n t i n r a t l i v e r (2013)
  • Author(s): Unuma K, A k i T, M a t s u d a S , F u n a k o s h i T, Yo s h i d a K , U e mu r a K
  • Journal Title: Hepatol Res Volume: 43(1) Pages: 91-6
• [Journal Article] Elimination and active extrusion of liver mitochondrial proteins during lipopolysaccharide administration in rat (2012)
  • Author(s): Unuma K, Aki T, Matsuda S, Funakoshi T, Yoshida KI, Uemura K
  • Journal Title: Hepatol Res Pages: 1
  • DOI: 10.1111/j.1872-034X.2012.01084.x.
• [Presentation] ヘムオキシゲナーゼ誘導剤は敗血症ラットの心筋障害をオートファジー活性化を介して軽減する (2013)
  • Author(s): 鵜沼香奈、秋利彦、船越丈司、内田恭子、則竹香菜子、藤井祐介、上村公一
  • Organizer: 97次日本法医学会総会
  • Year and Date: 20130000
• [Presentation] プロテオーム及びin vivo系を用いた敗血症における新たなバイオマーカーの同定 (2012)
  • Author(s): 鵜沼香奈,秋利彦,則竹香菜子,上村公一
  • Organizer: 96次日本法医学会総会
  • Year and Date: 20120000
• [Remarks] 東京医科歯科大学研究業績
  • URL: http://www.tmd.ac.jp/med/legm/gyouseki.html