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Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro

Saksida, Tamara; Nikolic, Ivana; Vujicic, Milica; Nilsson, Ulf LU ; Leffler, Hakon LU ; Lukic, Miodrag L.; Stojanovic, Ivana and Stosic-Grujicic, Stanislava (2013) In Journal of Cellular Physiology 228(7). p.1568-1576
Abstract
Beta cell apoptosis is a hallmark of diabetes. Since we have previously shown that galectin-3 deficient (LGALS3/) mice are relatively resistant to diabetes induction, the aim of this study was to examine whether beta cell apoptosis depends on the presence of galectin-3 and to delineate the underlying mechanism. Deficiency of galectin-3, either hereditary or induced through application of chemical inhibitors, -lactose or TD139, supported survival and function of islet beta cells compromised by TNF-+IFN-+IL-1 stimulus. Similarly, inhibition of galectin-3 by -lactose or TD139 reduced cytokine-triggered apoptosis of beta cells, leading to conclusion that endogenous galectin-3 propagates beta apoptosis in the presence of an inflammatory milieu.... (More)
Beta cell apoptosis is a hallmark of diabetes. Since we have previously shown that galectin-3 deficient (LGALS3/) mice are relatively resistant to diabetes induction, the aim of this study was to examine whether beta cell apoptosis depends on the presence of galectin-3 and to delineate the underlying mechanism. Deficiency of galectin-3, either hereditary or induced through application of chemical inhibitors, -lactose or TD139, supported survival and function of islet beta cells compromised by TNF-+IFN-+IL-1 stimulus. Similarly, inhibition of galectin-3 by -lactose or TD139 reduced cytokine-triggered apoptosis of beta cells, leading to conclusion that endogenous galectin-3 propagates beta apoptosis in the presence of an inflammatory milieu. Exploring apoptosis-related molecules expression in primary islet cells before and after treatment with cytokines we found that galectin-3 ablation affected the expression of major components of mitochondrial apoptotic pathway, such as BAX, caspase-9, Apaf, SMAC, caspase-3, and AIF. In contrast, anti-apoptotic molecules Bcl-2 and Bcl-XL were up-regulated in LGALS3/ islet cells when compared to wild-type (WT) counterparts (C57BL/6), resulting in increased ratio of anti-apoptotic versus pro-apoptotic molecules. However, Fas-triggered apoptotic pathway as well as extracellular signal-regulated kinase 1/2 (ERK1/2) was not influenced by LGALS-3 deletion. All together, these results point to an important role of endogenous galectin-3 in beta cell apoptosis in the inflammatory milieu that occurs during diabetes pathogenesis and implicates impairment of mitochondrial apoptotic pathway as a key event in protection from beta cell apoptosis in the absence of galectin-3. J. Cell. Physiol. 228: 15681576, 2013. (c) 2012 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cellular Physiology
volume
228
issue
7
pages
1568 - 1576
publisher
John Wiley & Sons
external identifiers
  • wos:000316681100023
  • scopus:84875509705
ISSN
1097-4652
DOI
10.1002/jcp.24318
language
English
LU publication?
yes
id
3bc193f8-8486-4b01-9e99-b35d1ae4cef1 (old id 3749579)
date added to LUP
2013-05-21 07:47:18
date last changed
2019-03-13 11:59:11
@article{3bc193f8-8486-4b01-9e99-b35d1ae4cef1,
  abstract     = {Beta cell apoptosis is a hallmark of diabetes. Since we have previously shown that galectin-3 deficient (LGALS3/) mice are relatively resistant to diabetes induction, the aim of this study was to examine whether beta cell apoptosis depends on the presence of galectin-3 and to delineate the underlying mechanism. Deficiency of galectin-3, either hereditary or induced through application of chemical inhibitors, -lactose or TD139, supported survival and function of islet beta cells compromised by TNF-+IFN-+IL-1 stimulus. Similarly, inhibition of galectin-3 by -lactose or TD139 reduced cytokine-triggered apoptosis of beta cells, leading to conclusion that endogenous galectin-3 propagates beta apoptosis in the presence of an inflammatory milieu. Exploring apoptosis-related molecules expression in primary islet cells before and after treatment with cytokines we found that galectin-3 ablation affected the expression of major components of mitochondrial apoptotic pathway, such as BAX, caspase-9, Apaf, SMAC, caspase-3, and AIF. In contrast, anti-apoptotic molecules Bcl-2 and Bcl-XL were up-regulated in LGALS3/ islet cells when compared to wild-type (WT) counterparts (C57BL/6), resulting in increased ratio of anti-apoptotic versus pro-apoptotic molecules. However, Fas-triggered apoptotic pathway as well as extracellular signal-regulated kinase 1/2 (ERK1/2) was not influenced by LGALS-3 deletion. All together, these results point to an important role of endogenous galectin-3 in beta cell apoptosis in the inflammatory milieu that occurs during diabetes pathogenesis and implicates impairment of mitochondrial apoptotic pathway as a key event in protection from beta cell apoptosis in the absence of galectin-3. J. Cell. Physiol. 228: 15681576, 2013. (c) 2012 Wiley Periodicals, Inc.},
  author       = {Saksida, Tamara and Nikolic, Ivana and Vujicic, Milica and Nilsson, Ulf and Leffler, Hakon and Lukic, Miodrag L. and Stojanovic, Ivana and Stosic-Grujicic, Stanislava},
  issn         = {1097-4652},
  language     = {eng},
  number       = {7},
  pages        = {1568--1576},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Cellular Physiology},
  title        = {Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro},
  url          = {http://dx.doi.org/10.1002/jcp.24318},
  volume       = {228},
  year         = {2013},
}