a Record control number WOS:000208700200003

a ISSN 1940-5901

a Original cataloging agency NEU GrandLibrary

a Language code of text/sound track or separate title eng

a Classification number W 20.5

b Item number .P74 2008

a Personal name Moran, Ana.

h Medium Electronic Document

a Title Prevention of Trauma and Hemorrhagic Shock-Mediated Liver Apoptosis by Activation of Stat3 alpha

c Statement of responsibility, etc Ana Moran, Ayse Akcan Arikan, Mary-Ann A.Mastrangelo, Yong Wu, Bi Yu, Valeria Poli, David J. Tweardy.

a Place of publication, distribution, etc E-Century Publishing Corp,

c Date of publication, distribution, etc 2008.

a Summary, etc Trauma is a major cause of mortality in the United States. Death among those surviving the initial insult is caused by multiple organ failure (MOF) with the liver among the organs most frequently affected. We previously demonstrated in rodents that trauma complicated by hemorrhagic shock (trauma/HS) results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required and the mechanism for the IL-6 protective effect have not been reported. In the experiments reported here, we demonstrated that the extent of liver apoptosis induced by trauma/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver apoptosis and is associated with increased Stat3 activation. Microarray analysis of the livers showed that the main effect of IL-6 was to normalize the trauma/HS-induced apoptosis transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver apoptosis and to normalize the trauma/HS-induced liver apoptosis transcriptome. Genetic deletion of a Stat3 beta, a naturally occurring, dominant-negative isoform of the Stat3, attenuated trauma/HS-induced liver apoptosis, confirming a role for Stat3, especially Stat3 alpha, in preventing trauma/HS-mediated liver apoptosis. Thus, trauma/HS-induced liver apoptosis depends on the duration of hypotension and requires resuscitation. IL-6 administration at the start of resuscitation reverses HS-induced liver apoptosis, through activation of Stat3 alpha, which normalizes the trauma/HS-induced liver apoptosis transcriptome.

a Topical term or geographic name as entry element Medicine, Experimental.

a Topical term or geographic name as entry element Near East University Article

a Topical term or geographic name as entry element Yakın Doğu Üniversitesi Makale

a Main entry heading International journal of clinical and experimental medicine

g Relationship information 2008 , Vol 1 Issue 3, p213-247

x International Standard Serial Number 19405901