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Ouabain Protects against Shiga Toxin-Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL

Burlaka, Ievgeniia ; Liu, Xiao Li ; Rebetz, Johan LU ; Arvidsson, Ida LU ; Yang, Liping ; Brismar, Hjalmar ; Karpman, Diana LU and Aperia, Anita (2013) In Journal of the American Society of Nephrology 24(9). p.1413-1423
Abstract
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-B 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... (More)
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-B 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-B 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. (Less)
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Contribution to journal
publication status
published
subject
in
Journal of the American Society of Nephrology
volume
24
issue
9
pages
1413 - 1423
publisher
American Society of Nephrology
external identifiers
  • wos:000325092900013
  • scopus:84884297830
  • pmid:23744887
ISSN
1046-6673
DOI
10.1681/ASN.2012101044
language
English
LU publication?
yes
id
b2bb9bd0-5782-4ae2-bd4d-46143d2ed279 (old id 4170464)
date added to LUP
2016-04-01 13:41:23
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2020-09-09 02:43:29
@article{b2bb9bd0-5782-4ae2-bd4d-46143d2ed279,
  abstract     = {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-B 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-B 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.},
  author       = {Burlaka, Ievgeniia and Liu, Xiao Li and Rebetz, Johan and Arvidsson, Ida and Yang, Liping and Brismar, Hjalmar and Karpman, Diana and Aperia, Anita},
  issn         = {1046-6673},
  language     = {eng},
  number       = {9},
  pages        = {1413--1423},
  publisher    = {American Society of Nephrology},
  series       = {Journal of the American Society of Nephrology},
  title        = {Ouabain Protects against Shiga Toxin-Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL},
  url          = {http://dx.doi.org/10.1681/ASN.2012101044},
  doi          = {10.1681/ASN.2012101044},
  volume       = {24},
  year         = {2013},
}