Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo(sarco)plasmic reticulum stress
Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP 3 ) formation, leading to an elevation in [Ca 2+ ] i released from the endo(sarco)plasmic reticulum (ER) to induce ER stress and perturbations of ER fun...
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Published in | Molecular and cellular biochemistry Vol. 361; no. 1-2; pp. 123 - 134 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.02.2012
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Our previous studies demonstrated that caclium-sensing receptor (CaR) stimulation elicited phospholipase C (PLC)-mediated inositol triphosphate (IP
3
) formation, leading to an elevation in [Ca
2+
]
i
released from the endo(sarco)plasmic reticulum (ER) to induce ER stress and perturbations of ER function, which cause cardiomyocyte apoptosis during ischemia/reperfusion (I/R). The aim of this study was to determine whether the protection of post-conditioning (PC) from I/R heart injury involved relieving calcium-sensing receptor (CaR)-induced ER stress. Male Wistar rats were subjected to 30 min of ischemia followed by 2 h of reperfusion. The rats were post-conditioned after the 30 min of ischemia by three cycles of 10 s of reperfusion followed by 10 s of ischemia at the onset of reperfusion. Meanwhile, GdCl
3
, an activator of CaR, and NPS-2390, a specific inhibitor, were administered. We found that the PC and PC with NPS-2390 groups improved the recovery of cardiac function during reperfusion compared to the IR and PC groups with GdCl
3
, respectively. [Ca
2+
]
i
and [Ca
2+
]
ER
were determined using Fluo-4 AM and Fluo-5N AM, respectively, using laser confocal microscopy. [Ca
2+
]
i
was significantly increased, whereas [Ca
2+
]
ER
was significantly decreased in the I/R and PC groups with GdCl
3
. The rate of apoptotic cells was significantly decreased as shown by TUNEL (Terminal deoxy-nucleotidyl transferase-mediated dUTP nick end labeling) assay in PC and PC with NPS-2390 groups compared to the I/R and PC groups with GdCl
3
. In the I/R and PC groups with GdCl
3
, the activated fragments of caspase-12, the cleavage products of activating transcription factor 6 (ATF6) and phospho-JNK (c-Jun NH
2
-terminal kinase) were increased compared to the PC and PC with GdCl
3
groups. These results demonstrated that PC could protect the myocardium from I/R injury by inhibiting CaR-induced sarcoplasmic reticulum stress. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0300-8177 1573-4919 |
DOI: | 10.1007/s11010-011-1096-7 |