Histone deacetylase as therapeutic target in a rodent model of hemorrhagic shock: Effect of different resuscitation strategies on lung and liver

摘要: Background DNA transcription is regulated in part by acetylation of nuclear histones, controlled 2 groups enzymes: histone deacetylases (HDAC) and acetyl transferases (HAT). We have shown previously that hemorrhage resuscitation are associated with HDAC/HAT imbalance, which influences the status cardiac histones. The goals this study were to determine whether: (1) after affects a fluid- organ-specific fashion; (2) administration HDAC inhibitors subsequent gene expression. Methods In first experiment, rats (n = 6/group) subjected volume-controlled resuscitated with: racemic lactated Ringer’s (DL-LR); L-lactated (L-LR); (3) 7.5% hypertonic saline (HTS); (4) ketone (KR); or (5) pyruvate (PR). Control included: (6) no (Sham); (7) (NR). second experiment 5/group), 3 inhibitors, valproic acid (VPA), trichostatin A (TSA), suberoylanilide hydroxamic (SAHA), added normal used as fluid for resuscitation. At end resuscitation, lung liver tissues subcellular protein fractionation Western blotting analyze acetylation. addition, cDNA microarrays RT-PCR measure expression selected genes. Results Hemorrhage did not change level lungs, whereas predominantly hyperacetylated An analysis on 10 lysine sites showed L-LR, HTS, KR caused largest number changes (7, 6, 6 respectively). SAHA 7 affected 57 genes (44 up, 13 down). Conclusions Resuscitation various fluids, well infusion pharmacologic fashion, even when administered post-insult limited period time. Uniquely metabolism, cellular growth, proliferation, differentiation, transformation, signaling.