Caspase-Independent Apoptosis Induced by Reperfusion Following Ischemia without Bile Duct Occlusion in Rat Liver
-
- Matsui Nobuaki
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
-
- Yoshioka Rie
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
-
- Nozawa Asako
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
-
- Kobayashi Naonobu
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
-
- Shichijo Yukari
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
-
- Yoshikawa Tadatoshi
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
-
- Akagi Masaaki
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University
この論文をさがす
抄録
<p>The contribution of caspases to hepatic ischemia/reperfusion (I/R)-induced apoptosis has not been completely understood yet. Several studies have demonstrated increased caspase activity during I/R and the protective effect of caspase inhibitors against I/R injuries. However, reports with opposing results also exist. Herein, we examined the contribution of caspases to the I/R-induced hepatic apoptosis in rats using caspase inhibitors and specific substrates of caspases. Hepatic I/R was induced via a 2-h occlusion of the portal vein and the hepatic artery, without conducting bile duct occlusion. DNA laddering and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL)-positive cells were increased at 3 h after reperfusion. Pretreatment with caspase inhibitors (Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-cmk) 2 or 10 mg/kg intravenously (i.v.), 20 mg/kg intraperitoneally (i.p.), Z-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-fmk) 3 mg/kg i.v.) failed to reduce apoptosis induced by I/R. Interestingly, apoptosis induced by the portal triad (hepatic artery, portal vein, and bile duct) occlusion/reperfusion could be marginally attenuated using Z-Asp-cmk (2 mg/kg i.v.). The cleavage activity for Ac-DEVD-α-(4-methylcoumaryl-7-amide) (MCA), a caspase-3/7/8/9 substrate, was significantly increased by I/R. Conversely, the cleavage activities for Ac-DNLD-MCA and MCA-VDQVDGW[K-DNP]-NH2, specific substrates for caspase-3 and -7 respectively, were decreased by I/R. Protein expression of the cellular inhibitor of apoptosis protein 2 (c-IAP2), an endogenous caspase inhibitor, was increased by ischemia. Nuclear translocation of the apoptosis-inducing factor (AIF), an initiator protein of caspase-independent apoptosis, was also increased during I/R. These results suggest that caspases are inhibited by c-IAP2 induced during ischemia and that AIF may be involved in initiation of apoptosis induced by hepatic I/R without bile duct occlusion.</p>
収録刊行物
-
- Biological & Pharmaceutical Bulletin
-
Biological & Pharmaceutical Bulletin 40 (1), 104-107, 2017
公益社団法人 日本薬学会
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1390282679609529600
-
- NII論文ID
- 130005188879
-
- NII書誌ID
- AA10885497
-
- ISSN
- 13475215
- 09186158
-
- NDL書誌ID
- 027819023
-
- PubMed
- 28049941
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可