The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling
Open accessAbstract
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.
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Cites
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221
Park, H. S., Jung, H. Y., Park, E. Y., Kim, J., Lee, W. J., & Bae, Y. S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3589 · Cited by 635
Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1
Tang, D., Shi, Y., Kang, R., Li, T., Xiao, W., Wang, H., & Xiao, X. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0806540 · Cited by 312
Cited by
ROS and the DNA damage response in cancer
Srinivas, U. S., Tan, B. W. Q., Vellayappan, B. A., & Jeyasekharan, A. D. (2019) · Redox Biology · doi:10.1016/j.redox.2018.101084 · Cited by 2,144
“The antioxidant N-acetylcysteine attenuates HMGB1 release [121], and HMGB1 release in itself increases ROS production [122], which can lead to further oxidation of HMGB1.”
BackgroundMechanisms of Cisplatin Nephrotoxicity
Miller, R. P., Tadagavadi, R. K., Ramesh, G., & Reeves, W. B. (2010) · Toxins · doi:10.3390/toxins2112490 · Cited by 1,622
HMGB1 is a therapeutic target for sterile inflammation and infection
Andersson, U., & Tracey, K. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101323 · Cited by 1,437
HMGB1 and RAGE in Inflammation and Cancer
Sims, G. P., Rowe, D. C., Rietdijk, S. T., Herbst, R., & Coyle, A. J. (2010) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132603 · Cited by 1,436
Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956
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Metadata
- Authors
- Tsung, A., Klune, J. R., Zhang, X., Jeyabalan, G., Cao, Z., Peng, X., Stolz, D. B., Geller, D. A., Rosengart, M. R., & Billiar, T. R.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2007-11-05
- Volume
- 204
- Issue
- 12
- Pages
- 2913-2923
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2106039427
- Cited by
- 620
- References
- 3
- FWCI
- 19.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Tsung, A., Klune, J. R., Zhang, X., Jeyabalan, G., Cao, Z., Peng, X., Stolz, D. B., Geller, D. A., Rosengart, M. R., & Billiar, T. R. (2007). HMGB1 release induced by liver ischemia involves Toll-like receptor 4–dependent reactive oxygen species production and calcium-mediated signaling. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20070247
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