Protective role of HSP72 against Clostridium difficile toxin A-induced intestinal epithelial cell dysfunction.

We determined whether the cytoprotective heat shock protein HSP72 protects against the injurious effects of Clostridium difficile toxin A (TxA) on intestinal epithelial cells. Colonic epithelial Caco-2/bbe (C2) cells were stably transfected with HSP72 antisense (C2AS) or vector only (C2VC), resulting in low and high HSP72 expression, respectively. Measurements of ...
epithelial barrier integrity, mitochondrial function, and apoptosis activation were assessed after TxA exposure. HSP72 and RhoA interactions were evaluated with immunoprecipitations. In C2AS cells, TxA was associated with a greater decrease in transepithelial resistance (TER), an increase in [(3)H]mannitol flux, and increased dissociation of perijunctional actin. Although HSP72 binds RhoA, it failed to prevent RhoA glucosylation. TxA caused a more rapid decrease in ATP, release of cytochrome c, and activation of caspase-9 in C2AS cells. To determine whether ATP depletion decreases TER, we treated cells with antimycin A, which caused a decline in TER. We conclude that HSP72 may protect intestinal epithelial cells from TxA-mediated damage through several mechanisms, including actin stabilization, mitochondrial protection, and inhibition of apoptosis activation, but not by prevention of RhoA glucosylation.
Mesh Terms:
Actins, Adenosine Triphosphate, Apoptosis, Bacterial Toxins, Caspase 9, Caspases, Cell Line, Enterotoxins, Enzyme Activation, Glycosylation, HSP72 Heat-Shock Proteins, Heat-Shock Proteins, Humans, Intestinal Mucosa, Mitochondria, Permeability, Precipitin Tests, Tight Junctions, rhoA GTP-Binding Protein
Am. J. Physiol., Cell Physiol.
Date: Apr. 01, 2003
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