Cardiac histones are substrates of histone deacetylase activity in hemorrhagic shock and resuscitation

Lin, Tom K.; Alam, Hasan B.; Chen, Huazhen; Britten-Webb, J.; Rhee, Peter; Kirkpatrick, John R.; Koustova, Elena

doi:10.1016/j.surg.2005.08.022

Cited by 51 publications

(36 citation statements)

References 24 publications

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“…HDACi's have also been tested in models of ischemia/reperfusion (88,89). Ischemia/reperfusion is essentially sterile inflammation, and, here, cytokines such as IL-1α and TNFα play a significant role.…”

Section: Treating Acute Diseases With Hdaci'smentioning

confidence: 99%

Histone Deacetylase Inhibitors for Treating a Spectrum of Diseases Not Related to Cancer

Dinarello

Fossati

Mascagni

2011

Mol Med

138

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This issue of Molecular Medicine contains 14 original research reports and state-of-the-art reviews on histone deacetylase inhibitors (HDACi's), which are being studied in models of a broad range of diseases not related to the proapoptotic properties used to treat cancer. The spectrum of these diseases responsive to HDACi's is for the most part due to several antiinflammatory properties, often observed in vitro but importantly also in animal models. One unifying property is a reduction in cytokine production as well as inhibition of cytokine postreceptor signaling. Distinct from their use in cancer, the reduction in inflammation by HDACi's is consistently observed at low concentrations compared with the higher concentrations required for killing tumor cells. This characteristic makes HDACi's attractive candidates for treating chronic diseases, since low doses are well tolerated. For example, low oral doses of the HDACi givinostat have been used in children to reduce arthritis and are well tolerated. In addition to the antiinflammatory properties, HDACi's have shown promise in models of neurodegenerative disorders, and HDACi's also hold promise to drive HIV-1 out of latently infected cells. No one molecular mechanism accounts for the non-cancer-related properties of HDACi's, since there are 18 genes coding for histone deacetylases. Rather, there are mechanisms unique for the pathological process of specific cell types. In this overview, we summarize the preclinical data on HDACi's for therapy in a wide spectrum of diseases unrelated to the treatment of cancer. The data suggest the use of HDACi's in treating autoimmune as well as chronic inflammatory diseases.

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Section: Treating Acute Diseases With Hdaci'smentioning

confidence: 99%

Histone Deacetylase Inhibitors for Treating a Spectrum of Diseases Not Related to Cancer

Dinarello

Fossati

Mascagni

2011

Mol Med

138

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“…In rats subjected to hemorrhagic shock and subsequent resuscitation, partial deacetylation of histones in cardiac tissue was apparent [103]. Addition of HDACi TSA, VPA and SAHA to the resuscitation fluid reversed the shockinduced changes to histone acetylation, with SAHA being the most effective [103].…”

Section: Trauma/hemorrhage/shockmentioning

confidence: 99%

“…Addition of HDACi TSA, VPA and SAHA to the resuscitation fluid reversed the shockinduced changes to histone acetylation, with SAHA being the most effective [103]. The induction of shock itself is thought to cause an imbalance in HAT/HDAC activity; the net result favours HDAC activity, with HDACi partly correcting this imbalance.…”

Section: Trauma/hemorrhage/shockmentioning

confidence: 99%

Histone Deacetylase Inhibitors In Inflammatory Disease

Halili¹,

Andrews²,

Sweet³

et al. 2009

CTMC

178

153

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Lysine acetylation is becoming increasingly appreciated as a key post-translational modification in the endogenous regulation of protein function. The so-called histone acetyl transferases (HATs) and histone deacetylases (HDACs), best known for their roles in controlling chromatin remodeling via histone acetylation/deacetylation, are now known to modify a large number of non-histone proteins to control diverse cell processes. In relation to inflammation, acetylation modulates the activity or function of cytokine receptors, nuclear hormone receptors, intracellular signaling molecules and transcription factors. Small molecule inhibitors of HDACs have been found to trigger both pro- and anti-inflammatory effects in a range of inflammation-relevant cell types. Although their inflammatory profiles have only just begun to be elucidated, some HDAC inhibitors are already showing therapeutic promise in animal models of inflammatory diseases such as arthritis, inflammatory bowel diseases, septic shock, ischemia-reperfusion injury, airways inflammation and asthma, diabetes, age-related macular degeneration, cardiovascular diseases, multiple sclerosis and other CNS and neurodegenerative diseases. This article describes those HDAC inhibitors which have been most examined to date for their potentially beneficial effects on inflammatory cells or in animal models of inflammatory disease.

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“…23 We have previously shown that hemorrhage is associated with an imbalance in HDAC/HAT activity, with overall histone hypoacetylation, which is further modulated by resuscitation in a fluid-specific fashion. 24 Histone acetylation patterns after hemorrhagic shock and resuscitation are conserved across species (rodents and swine), and an increase in histone acetylation translates into enhanced transcription of early-acute response genes. 25 Furthermore, addition of HDACI to the resuscitation fluid increases histone acetylation, and upregulates the transcription of key regulatory genes.…”

mentioning

confidence: 99%

“…25 Furthermore, addition of HDACI to the resuscitation fluid increases histone acetylation, and upregulates the transcription of key regulatory genes. 24,26 Additionally, pre-shock treatment with HDACI, in the absence of fluid resuscitation, corrects shock-induced alterations in the histone acetylation pattern, protects organs, 27 and improves survival. 28 The goal of the current study was to test whether post-shock administration of HDACI, in the absence of fluid resuscitation, would improve early survival in a lethal model of hemorrhagic shock.…”

mentioning

confidence: 99%