Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models

Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models

Bax and Bak, two pro-apoptotic Bcl-2 family proteins, have been implicated in acute kidney injury following renal ischemia/reperfusion; however, definitive evidence for a role of these genes in the disease process is lacking. Here we first examined two Bax-deficient mouse models and found that only...

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Main Authors: Wei, Qingqing, Dong, Guie, Chen, Jian-Kang, Ramesh, Ganesan, Dong, Zheng
Format: Online
Language:English
Published: 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686831/
id pubmed-3686831
recordtype oai_dc
spelling pubmed-36868312014-01-01 Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models Wei, Qingqing Dong, Guie Chen, Jian-Kang Ramesh, Ganesan Dong, Zheng Article Bax and Bak, two pro-apoptotic Bcl-2 family proteins, have been implicated in acute kidney injury following renal ischemia/reperfusion; however, definitive evidence for a role of these genes in the disease process is lacking. Here we first examined two Bax-deficient mouse models and found that only conditional Bax-deletion specifically from proximal tubules could ameliorate ischemic acute kidney injury. Global (whole mouse) knockout of Bax enhanced neutrophil infiltration without significant effect on kidney injury. In contrast, global knockout of Bak protected mice from ischemic acute kidney injury with improved renal function. Interestingly, in these models, Bax or Bak knockout attenuated renal tubular cell apoptosis without significantly affecting necrotic tubular damage. Cytochrome c release in ischemic acute kidney injury was also suppressed in conditional Bax or global Bak-knockout mice. In addition, Bak deficiency prevented mitochondrial fragmentation in ischemic acute kidney injury. Thus, our gene-knockout studies support a critical role of Bax and Bak in tubular cell apoptosis in ischemic acute kidney. Furthermore, necrosis and apoptosis have distinguishable regulatory functions. 2013-03-06 2013-07 /pmc/articles/PMC3686831/ /pubmed/23466994 http://dx.doi.org/10.1038/ki.2013.68 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Wei, Qingqing
Dong, Guie
Chen, Jian-Kang
Ramesh, Ganesan
Dong, Zheng
spellingShingle Wei, Qingqing
Dong, Guie
Chen, Jian-Kang
Ramesh, Ganesan
Dong, Zheng
Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
author_facet Wei, Qingqing
Dong, Guie
Chen, Jian-Kang
Ramesh, Ganesan
Dong, Zheng
author_sort Wei, Qingqing
title Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
title_short Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
title_full Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
title_fullStr Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
title_full_unstemmed Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
title_sort bax and bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models
description Bax and Bak, two pro-apoptotic Bcl-2 family proteins, have been implicated in acute kidney injury following renal ischemia/reperfusion; however, definitive evidence for a role of these genes in the disease process is lacking. Here we first examined two Bax-deficient mouse models and found that only conditional Bax-deletion specifically from proximal tubules could ameliorate ischemic acute kidney injury. Global (whole mouse) knockout of Bax enhanced neutrophil infiltration without significant effect on kidney injury. In contrast, global knockout of Bak protected mice from ischemic acute kidney injury with improved renal function. Interestingly, in these models, Bax or Bak knockout attenuated renal tubular cell apoptosis without significantly affecting necrotic tubular damage. Cytochrome c release in ischemic acute kidney injury was also suppressed in conditional Bax or global Bak-knockout mice. In addition, Bak deficiency prevented mitochondrial fragmentation in ischemic acute kidney injury. Thus, our gene-knockout studies support a critical role of Bax and Bak in tubular cell apoptosis in ischemic acute kidney. Furthermore, necrosis and apoptosis have distinguishable regulatory functions.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686831/
_version_ 1611987602157600768

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