Inhibition of histone deacetylase 6 improves long-term survival in a lethal septic model

The Journal of Trauma and Acute Care Surgery
Yongqing LiHasan B Alam

Abstract

We recently demonstrated that suberoylanilide hydroxamic acid, a broad-spectrum histone deacetylase (HDAC) inhibitor that inhibits HDACs 1, 2, 3, and 6, improves survival in a mouse model of cecal ligation and puncture (CLP)-induced lethal sepsis. The current study was undertaken to determine the effect of selective inhibition of HDAC isoform on survival, key cytokine production, organ injury, bacteria clearance, and cell apoptosis. In Experiment 1, C57BL/6J mice were subjected to CLP and, 1 hour later, given intraperitoneal injections of (1) Tubastatin A (inhibitor of HDAC6) dissolved in dimethyl sulfoxide (DMSO), (2) MS-275 (inhibitor of HDACs 1, 2, and 3) in DMSO, and (3) DMSO only. Survival was monitored for 10 days. In Experiment 2, 1 hour after CLP, animals were treated with DMSO vehicle or Tubastatin A. Sham-operated animals served as control. Peritoneal fluid and blood samples were collected for measurement of cytokines at 24 hours or 48 hours. Blood at 48 hours was also used to determine bacteria load. Liver was harvested to evaluate acute liver injury. In Experiment 3, Primary splenocytes were used to assess cytokine responses and phagocytosis. Macrophages were cultured and harvested 3 hours and 6 hours after lipopoly...Continue Reading

References

Mar 12, 2003·Cell·Thorsten CramerRandall S Johnson
Apr 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Stephen J HaggartyStuart L Schreiber
Oct 24, 2007·Molecular Cancer Research : MCR·Milos DokmanovicPaul A Marks
May 13, 2008·Trends in Cell Biology·Agustín Valenzuela-FernándezFrancisco Sánchez-Madrid
Feb 9, 2010·Nature Chemical Biology·James E BradnerRalph Mazitschek
Mar 3, 2010·Genes & Development·Teppei YamaguchiPatrick Matthias
Jul 2, 2010·The New England Journal of Medicine·Richard S Hotchkiss, Steven Opal
Jul 10, 2010·Journal of the American Chemical Society·Kyle V ButlerAlan P Kozikowski
Aug 13, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Reinhard GrausenburgerWilfried Ellmeier
Sep 8, 2010·Nature Immunology·Scott B BergerCox Terhorst
May 17, 2011·Trends in Immunology·Melanie R ShakespearMatthew J Sweet
Nov 16, 2011·Immunology and Cell Biology·Bandar Ali SulimanBryan R G Williams
May 24, 2012·The New England Journal of Medicine·V Marco RanieriUNKNOWN PROWESS-SHOCK Study Group
May 24, 2013·Biochemical Society Transactions·Sarah HawtreeAnthony G Wilson
Jul 23, 2014·The Journal of Trauma and Acute Care Surgery·Ting ZhaoHasan B Alam

❮ Previous
Next ❯

Citations

Oct 31, 2015·The Journal of Trauma and Acute Care Surgery·Zhusheng FengWen Yin
Feb 18, 2016·Pathogens and Disease·Chifu B HuangJeffrey L Ebersole
Oct 31, 2015·The Journal of Trauma and Acute Care Surgery·Martin SillesenHasan B Alam
Oct 23, 2015·The Journal of Trauma and Acute Care Surgery·Ting ZhaoHasan B Alam
Oct 30, 2016·Antioxidants & Redox Signaling·Marten A Hoeksema, Menno P de Winther
Feb 6, 2018·The Journal of Trauma and Acute Care Surgery·Panpan ChangHasan B Alam
Oct 4, 2017·Critical Reviews in Microbiology·Aleksander M Grabiec, Jan Potempa
Nov 9, 2016·The Journal of Pharmacology and Experimental Therapeutics·Anh DoAbishek Iyer
May 18, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jinyan YuJian Fu
Aug 10, 2019·Anesthesia and Analgesia·Ettore CrimiClaudio Napoli
Jan 3, 2019·Shock·Aaron M WilliamsHasan B Alam
Jan 19, 2019·International Journal of Molecular Sciences·Andreas von Knethen, Bernhard Brüne
Jan 6, 2017·American Journal of Physiology. Renal Physiology·Yingfeng ShiNa Liu
Nov 4, 2016·Nature Reviews. Drug Discovery·David F ToughRab K Prinjha
Oct 31, 2019·Cellular & Molecular Immunology·Siyuan ChenXiawei Wei
Aug 24, 2018·Molecular Medicine·Ben KeLiping Yang
Jul 27, 2018·Inflammation·Qiufang DengYongqing Li
Apr 14, 2020·The Journal of Trauma and Acute Care Surgery·Rachel RussoHasan B Alam
Sep 10, 2020·Frontiers in Pharmacology·Sergi Herve AkoneRolf Müller
Mar 21, 2020·The Journal of Trauma and Acute Care Surgery·Ben E BiesterveldHasan B Alam
Oct 6, 2020·American Journal of Physiology. Renal Physiology·Wei ZhangShougang Zhuang
Nov 26, 2020·Molecular Genetics & Genomic Medicine·Xuan GuoCaiyan Zhao
Dec 17, 2020·Frontiers in Pharmacology·Maria Gracia-HernandezAlejandro Villagra

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis