title: Modulation of acetylation: creating a pro-survival and anti-inflammatory phenotype in lethal hemorrhagic and septic shock.
abstract: Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histone and nonhistone proteins and in regulating fundamental cellular activities. In this paper we review and discuss intriguing recent developments in the use of histone deacetylase inhibitors (HDACIs) to combat some critical conditions in an animal model of hemorrhagic and septic shock. HDACIs have neuroprotective, cardioprotective, renal-protective, and anti-inflammatory properties; survival improvements have been significantly shown in these models. We discuss the targets and mechanisms underlying these effects of HDACIs and comment on the potential new clinical applications for these agents in the future. This paper highlights the emerging roles of HDACIs as acetylation modulators in models of hemorrhagic and septic shock and explains some contradictions encountered in previous studies.
authors.affiliation: Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, 165 Cambridge Street, Suite 810, Boston, MA 02114, USA.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Li
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D057890:Epigenomics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000037:antagonists & inhibitors; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000201:enzymology; D012772:Shock, Septic / Q000188:drug therapy* / Q000201:enzymology; D013552:Swine
chemical_list: D018797:Cell Cycle Proteins; D018840:HSP70 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006657:Histones; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; C474831:TRIB3 protein, human; C494929:PTEN protein, human