HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling.

HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. Research Abstract Details 

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HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. Abstract Text:

Allan Tsung,John R Klune,Xianghong Zhang,Geetha Jeyabalan,Zongxian Cao,Ximei Peng,Donna B Stolz,David A Geller,Matthew R Rosengart,Timothy R Billiar,Allan Tsung,John R Klune,Xianghong Zhang,Geetha Jeyabalan,Zongxian Cao,Ximei Peng,Donna B Stolz,David A Geller,Matthew R Rosengart,Timothy R Billiar,

Ischemic tissues require mechanisms to alert the immune system of impending cell damage. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. We elucidate the mechanism by which HMGB1, one of the key alarm molecules released during liver ischemia/reperfusion (I/R), is mobilized in response to hypoxia. HMGB1 release from cultured hepatocytes was found to be an active process regulated by reactive oxygen species (ROS). Optimal production of ROS and subsequent HMGB1 release by hypoxic hepatocytes required intact Toll-like receptor (TLR) 4 signaling. To elucidate the downstream signaling pathways involved in hypoxia-induced HMGB1 release from hepatocytes, we examined the role of calcium signaling in this process. HMGB1 release induced by oxidative stress was markedly reduced by inhibition of calcium/calmodulin-dependent kinases (CaMKs), a family of proteins involved in a wide range of calcium-linked signaling events. In addition, CaMK inhibition substantially decreased liver damage after I/R and resulted in accumulation of HMGB1 in the cytoplasm of hepatocytes. Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling.

HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. Publishing Authors By Initials

A Tsung,JR Klune,X Zhang,G Jeyabalan,Z Cao,X Peng,DB Stolz,DA Geller,MR Rosengart,TR Billiar,A Tsung,JR Klune,X Zhang,G Jeyabalan,Z Cao,X Peng,DB Stolz,DA Geller,MR Rosengart,TR Billiar,

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HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of experimental medicine

VOLUME: 204

Page Numbers: 2913-23

Journal Abbreviation: J. Exp. Med.

ISSN: 1540-9538

DAY: 5

MONTH: 11

YEAR: 2007

HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. Information

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LANGUAGE: eng

NlmUniqueID: 2985109

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Grant and Affiliation Information for HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling.

AFFILIATION: Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: R01-GM52021

ACRONYM: GM

MEDLINETA: J Exp Med

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