title: Potassium Acetate Blocks Clostridium difficile Toxin A-Induced Microtubule Disassembly by Directly Inhibiting Histone Deacetylase 6, Thereby Ameliorating Inflammatory Responses in the Gut.
abstract: Clostridium difficile toxin A is known to cause deacetylation of tubulin proteins, which blocks microtubule formation and triggers barrier dysfunction in the gut. Based on our previous finding that the Clostridium difficile toxin A-dependent activation of histone deacetylase 6 (HDAC-6) is responsible for tubulin deacetylation and subsequent microtubule disassembly, we herein examined the possible effect of potassium acetate (PA; whose acetyl group prevents the binding of tubulin to HDAC-6) as a competitive/false substrate. Our results revealed that PA inhibited toxin A-induced deacetylation of tubulin and recovered toxin A-induced microtubule disassembly. In addition, PA treatment significantly decreased the production of IL-6 (a marker of inflamed tissue) in the toxin A-induced mouse enteritis model. An in vitro HDAC assay revealed that PA directly inhibited HDAC-6-mediated tubulin deacetylation, indicating that PA acted as a false substrate for HDAC-6. These results collectively indicate that PA treatment inhibits HDAC-6, thereby reducing the cytotoxicity and inflammatory responses caused by C. difficile toxin A.
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.|Hainan Institute of Science and Technology, Haikou 571126, P.R. China.
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Lu
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
authors.forename: Dae Hong
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
authors.forename: Ik Hwan
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
authors.forename: I Na
authors.initials: IN
authors.lastname: Yoon
authors.affiliation: Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Jeonju 54875, Republic of Korea.
authors.forename: Jae Sam
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D003092:Colitis / Q000188:drug therapy; D003106:Colon / Q000166:cytology / Q000187:drug effects; D004195:Disease Models, Animal; D004751:Enteritis / Q000188:drug therapy; D004768:Enterotoxins / Q000633:toxicity*; D019073:HT29 Cells; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D019347:Potassium Acetate / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D056572:Histone Deacetylase Inhibitors; D015850:Interleukin-6; D014404:Tubulin; C577686:interleukin-6, mouse; C041348:tcdA protein, Clostridium difficile; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D019347:Potassium Acetate
keywords: Clostridium difficile toxin A; colitis; enteritis; histone deacetylase 6; microtubule assembly with tubulin; potassium acetate