The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity
Aims: The aim of this study was to determine whether calpain is involved in Cl- -induced myocardial ischemia/reperfusion (I/R) injury. Methods: Isolated rat hearts were subjected to either 45 min of global no-flow ischemia followed by reperfusion or successive perfusion with Ca2+ -free KH solution f...
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doaj-cf70a736fe7d4c1ca20dfad2a8ab87da2020-11-25T03:26:42ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-04-013562121213410.1159/000374018374018The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain ActivityJian-Ying ZhangFeng WuXiao-Ming GuZhen-Xiao JinLing-Heng KongYuan ZhangJing-Jun ZhouFeng GaoAims: The aim of this study was to determine whether calpain is involved in Cl- -induced myocardial ischemia/reperfusion (I/R) injury. Methods: Isolated rat hearts were subjected to either 45 min of global no-flow ischemia followed by reperfusion or successive perfusion with Ca2+ -free KH solution for 3 min and normal KH solution for 30 min, also known as Ca2+ paradox. Results: The hearts in the I/R group exhibited increases in myocardial injury area, LDH release, caspase 3 activity and apoptotic indices and a marked decline in cardiac performance. As was the case regarding the effects of MDL 28170, an inhibitor of calpain, treatment with 5 µM NPPB, 5 µM DIDS and low Cl- significantly attenuated cardiac injury. Moreover, each of the treatments significantly protected against Ca2+ overload-induced injury in the setting of Ca2+ paradox. The Western blot and immunofluorescence data revealed that there was an increase in the percentages of calpain membrane-positive cells and the numbers of fragments resulting from the calpain-mediated proteolysis of α-fodrin in both the I/R and the Ca2+ paradox, indicating that the activation of calpain occurred. More importantly, these effects were mitigated by the blockade of transmembrane Cl- flux, as was accomplished via MDL 28170. Conclusion: Our results provide evidence that the blockade of transmembrane Cl- flux mitigates I/R-induced cardiac injury via the inhibition of calpain activity. They also indicate that intracellular Ca2+ overload regulates calpain activation in the setting of Cl- -induced injury.http://www.karger.com/Article/FullText/374018ChlorideCalpainHeartCalciumIschemia/Reperfusion |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian-Ying Zhang Feng Wu Xiao-Ming Gu Zhen-Xiao Jin Ling-Heng Kong Yuan Zhang Jing-Jun Zhou Feng Gao |
spellingShingle |
Jian-Ying Zhang Feng Wu Xiao-Ming Gu Zhen-Xiao Jin Ling-Heng Kong Yuan Zhang Jing-Jun Zhou Feng Gao The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity Cellular Physiology and Biochemistry Chloride Calpain Heart Calcium Ischemia/Reperfusion |
author_facet |
Jian-Ying Zhang Feng Wu Xiao-Ming Gu Zhen-Xiao Jin Ling-Heng Kong Yuan Zhang Jing-Jun Zhou Feng Gao |
author_sort |
Jian-Ying Zhang |
title |
The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity |
title_short |
The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity |
title_full |
The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity |
title_fullStr |
The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity |
title_full_unstemmed |
The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity |
title_sort |
blockade of transmembrane cl- flux mitigates i/r-induced heart injury via the inhibition of calpain activity |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2015-04-01 |
description |
Aims: The aim of this study was to determine whether calpain is involved in Cl- -induced myocardial ischemia/reperfusion (I/R) injury. Methods: Isolated rat hearts were subjected to either 45 min of global no-flow ischemia followed by reperfusion or successive perfusion with Ca2+ -free KH solution for 3 min and normal KH solution for 30 min, also known as Ca2+ paradox. Results: The hearts in the I/R group exhibited increases in myocardial injury area, LDH release, caspase 3 activity and apoptotic indices and a marked decline in cardiac performance. As was the case regarding the effects of MDL 28170, an inhibitor of calpain, treatment with 5 µM NPPB, 5 µM DIDS and low Cl- significantly attenuated cardiac injury. Moreover, each of the treatments significantly protected against Ca2+ overload-induced injury in the setting of Ca2+ paradox. The Western blot and immunofluorescence data revealed that there was an increase in the percentages of calpain membrane-positive cells and the numbers of fragments resulting from the calpain-mediated proteolysis of α-fodrin in both the I/R and the Ca2+ paradox, indicating that the activation of calpain occurred. More importantly, these effects were mitigated by the blockade of transmembrane Cl- flux, as was accomplished via MDL 28170. Conclusion: Our results provide evidence that the blockade of transmembrane Cl- flux mitigates I/R-induced cardiac injury via the inhibition of calpain activity. They also indicate that intracellular Ca2+ overload regulates calpain activation in the setting of Cl- -induced injury. |
topic |
Chloride Calpain Heart Calcium Ischemia/Reperfusion |
url |
http://www.karger.com/Article/FullText/374018 |
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