potassium-acetate and Disease-Models--Animal

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.

Topics: Animals; Bacterial Toxins; Colitis; Colon; Disease Models, Animal; Enteritis; Enterotoxins; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Histone Deacetylases; HT29 Cells; Humans; Inflammation; Interleukin-6; Male; Mice; Potassium Acetate; Tubulin

Experimentally induced heterotopia exhibit many of the anatomical features characteristic of cortical malformations in children with early-onset epilepsy. We used extracellular field potential recordings from the dorsal hippocampus of intact adult rats to determine whether the excitability of CA1 pyramidal cells was enhanced in rats with experimentally induced hippocampal dysplasia. Electrical stimulation of afferent fibers resulted in more robust population responses in the CA1 region of methylazoxymethanol (MAM)-treated rats vs the controls. The local population of CA1 pyramidal neurons was more excitable in the MAM-treated rat than in the control animals after synaptic activation. These results suggest that the excitability of the CA1 region in rats with hippocampal dysplasia is greater than that in control animals.

Topics: Animals; Bicuculline; Disease Models, Animal; Dose-Response Relationship, Radiation; Electric Stimulation; Epilepsy; Evoked Potentials; Female; GABA Antagonists; Hippocampus; Male; Methylazoxymethanol Acetate; Neurons; Potassium Acetate; Pregnancy; Rats; Rats, Sprague-Dawley