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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4170464
- author
- Burlaka, Ievgeniia
; Liu, Xiao Li
; Rebetz, Johan
LU
; Arvidsson, Ida
LU
; Yang, Liping
; Brismar, Hjalmar
; Karpman, Diana
LU
and Aperia, Anita
- organization
- publishing date
- 2013
- type
- 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
- date last changed
- 2022-04-06 06:27:56
@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}},
}