Ouabain protects against Shiga toxin-triggered apoptosis by reversing the imbalance between Bax and Bcl-xL.

Burlaka I, Liu XL, Rebetz J, Arvidsson I, Yang L, Brismar H, Karpman D, Aperia A

J. Am. Soc. Nephrol. 24 (9) 1413-1423 [2013-09-00; online 2013-06-06]

Hemolytic uremic syndrome, a life-threatening disease often accompanied by acute renal failure, usually occurs after gastrointestinal infection with Shiga toxin 2 (Stx2)-producing Escherichia coli. Stx2 binds to the glycosphingolipid globotriaosylceramide receptor, expressed by renal epithelial cells, and triggers apoptosis by activating the apoptotic factor Bax. Signaling via the ouabain/Na,K-ATPase/IP3R/NF-κB pathway increases expression of Bcl-xL, an inhibitor of Bax, suggesting that ouabain might protect renal cells from Stx2-triggered apoptosis. Here, exposing rat proximal tubular cells to Stx2 in vitro resulted in massive apoptosis, upregulation of the apoptotic factor Bax, increased cleaved caspase-3, and downregulation of the survival factor Bcl-xL; co-incubation with ouabain prevented all of these effects. Ouabain activated the NF-κB antiapoptotic subunit p65, and the inhibition of p65 DNA binding abolished the antiapoptotic effect of ouabain in Stx2-exposed tubular cells. Furthermore, in vivo, administration of ouabain reversed the imbalance between Bax and Bcl-xL in Stx2-treated mice. Taken together, these results suggest that ouabain can protect the kidney from the apoptotic effects of Stx2.

Affiliated researcher

PubMed 23744887

DOI 10.1681/ASN.2012101044

Crossref 10.1681/ASN.2012101044

pii: ASN.2012101044
pmc: PMC3752948

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