{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T12:27:17Z","timestamp":1777552037963,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T00:00:00Z","timestamp":1171411200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> Apoptosis is involved in hepatic ischemia\/reperfusion injury. The protein FNK, constructed from an anti\u2010apoptotic protein Bcl\u2010x<jats:sub>L<\/jats:sub>, exhibits the stronger anticell death activity. We evaluated the effect of FNK on apoptosis after hepatic ischemia and reperfusion, using FNK\u2010overexpressing transgenic mice and the HIV\/Tat protein\u2010transduction\u2010domain (PTD) that mediates the introduction of FNK into cells when fused with FNK (PTD\u2010FNK).<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Mice were given hepatic ischemic insult for 90\u2003min followed by reperfusion for 3 h. FNK overexpression was determined by immunohistochemistry and Western blot. PTD\u2010FNK was intraperitoneally injected into wild mice 3\u2003h\u2003before the insult. Liver injury was determined by the caspase activation, DNA fragmentation, and hematoxylin\u2013eosin and terminal deoxynucleotidyl transferase\u2010mediated dUTP\u2010 digoxigenin nick\u2010end labelling (TUNEL) stainings.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> In FNK\u2010transgenic mice, FNK overexpression inhibited the activation of caspase 3\/caspase 3\u2010like activity and DNA fragmentation caused by the injury. In wild mice preinjected with PTD\u2010FNK, PTD\u2010FNK significantly inhibited the caspase activation and DNA fragmentation, reduced the area of liver vacuolization, and protected hepatic cells surrounding blood vessels, irrespective of central or portal veins, from the ischemia\/reperfusion damage.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> FNK inhibits apoptotic death due to the ischemia\/reperfusion injury. Our results provide the reasonable expectation of therapeutic protein PTD\u2010FNK for clinical applications, such as transplantation, to protect against ischemia\/reperfusion injury.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2007.00022.x","type":"journal-article","created":{"date-parts":[[2010,9,15]],"date-time":"2010-09-15T13:40:50Z","timestamp":1284558050000},"page":"133-142","source":"Crossref","is-referenced-by-count":20,"title":["Protection of hepatic cells from apoptosis induced by ischemia\/reperfusion injury by protein therapeutics"],"prefix":"10.1111","volume":"37","author":[{"given":"Shinya","family":"Nagai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadamitsu","family":"Asoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujiro","family":"Shidara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misao","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukichi","family":"Moriyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Ohta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,2,14]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(02)03465-6"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2388(199605\/06)12:3<179::AID-SSU6>3.0.CO;2-4"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4800(91)90005-I"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840160521"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00259-8"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.2.253"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.22002"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199904270-00003"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(03)00074-9"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005841200"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.262460299"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.11.144"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401569"},{"key":"e_1_2_5_15_2","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1182\/blood.V88.3.995.995","article-title":"Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c\u2010kit receptor tyrosine kinase","volume":"88","author":"Kitayama H","year":"1996","journal-title":"Blood"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00321-2"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00485-1"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-022X(02)00052-0"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300513"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199806150-00004"},{"key":"e_1_2_5_21_2","first-page":"265","volume-title":"The Liver. 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