Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3749579
- author
- Saksida, Tamara ; Nikolic, Ivana ; Vujicic, Milica ; Nilsson, Ulf LU ; Leffler, Hakon LU ; Lukic, Miodrag L. ; Stojanovic, Ivana and Stosic-Grujicic, Stanislava
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Cellular Physiology
- volume
- 228
- issue
- 7
- pages
- 1568 - 1576
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000316681100023
- scopus:84875509705
- ISSN
- 1097-4652
- DOI
- 10.1002/jcp.24318
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Division of Microbiology, Immunology and Glycobiology - MIG (013025200)
- id
- 3bc193f8-8486-4b01-9e99-b35d1ae4cef1 (old id 3749579)
- date added to LUP
- 2016-04-01 10:28:48
- date last changed
- 2022-02-17 18:29:57
@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 Inc.}},
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}},
doi = {{10.1002/jcp.24318}},
volume = {{228}},
year = {{2013}},
}