{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:07:14Z","timestamp":1790910434040,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3714,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>\n                                 <jats:bold>The p8 protein is a transcription factor that regulates the expression of genes involved in cell defense against the adverse effects of stress. Its expression is strongly, rapidly, and transiently induced in most cells on exposure to various stress agents. This study assessed the role of p8 in the response of the liver to CCl4-induced injury. We found that p8 was indeed overexpressed in the liver after CCl4 administration. Hepatic injury following CCl4 injection was monitored in wild-type and p8\u2212\/\u2212 mice. Serum alanine and aspartate aminotransferase activities were higher and peaked earlier in p8\u2212\/\u2212 mice than in wild-type mice, which is in agreement with the observation of significantly larger areas of necrosis in p8\u2212\/\u2212 liver. Absence of p8 expression is therefore associated with increased liver sensitivity to CCl4. In fact, CCl4 toxicity is mediated by derivatives generated by its conversion by the enzyme CYP2E1. It is known that CYP2E1 is downregulated in the liver during the first hours following CCl4 administration as part of a self-defense mechanism. We found that CYP2E1 downregulation was significantly delayed in p8\u2212\/\u2212 liver compared with wild-type liver, allowing increased production of toxic CCl4 derivatives.<\/jats:bold>\n                                 <jats:underline>In conclusion<\/jats:underline>\n                                 <jats:bold>, inactivation of the p8 gene increases liver sensitivity to CCl4, as it appears to delay the triggering of CYP2E1 downregulation. The p8 protein is therefore an important element of hepatocyte stress response. (Hepatology 2005;42:176\u2013182.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20759","type":"journal-article","created":{"date-parts":[[2005,6,16]],"date-time":"2005-06-16T22:50:46Z","timestamp":1118962246000},"page":"176-182","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":42,"title":["Inactivation of Stress Protein p8 Increases Murine Carbon Tetrachloride Hepatotoxicity via Preserved CYP2E1 Activity *"],"prefix":"10.1097","volume":"42","author":[{"given":"David","family":"Ta\u00efeb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Malicet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palma","family":"Rocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Arnaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Dagorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan 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