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KMID : 0545120160260040693
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Journal of Microbiology and Biotechnology
2016 Volume.26 No. 4 p.693 ~ p.699
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Potassium Acetate Blocks Clostridium difficile Toxin A-Induced Microtubule Disassembly by Directly Inhibiting Histone Deacetylase 6, Thereby Ameliorating Inflammatory Responses in the Gut
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Lu Li Fang
Kim Dae-Hong
Lee Ik-Hwan
Hong Ji
Zhang Peng
Yoon I-Na
Hwang Jae-Sam
Kim Ho
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Abstract
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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.
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KEYWORD
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Clostridium difficile toxin A, colitis, microtubule assembly with tubulin, potassium acetate, enteritis, histone deacetylase 6
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