Abstract |
Recent studies suggest that besides the L-type calcium channel, two calcium channels on the endoplasmic reticulum (ER), the inositol 1,4,5-trisphosphate receptor (InsP3R) and ryanodine receptor (RyR), may play a role in the apoptotic process of renal tubular cells induced by ischemia/reperfusion (I/R) injury. We used antimycin A to induce cell I/R injury in vitro and found an elevation of the cytosolic calcium concentration and consequently apoptosis. Blocking either the L-type calcium channel with nicardipine or the InsP3R with TMB-8 can inhibit cytochrome c release, activate caspase 3 and decrease the apoptotic cell number. However, blocking the RyR with dantrolene had no effect. We further found that Ca(2+) influx through the L-type channel is needed for the opening of the InsP3R which activates a cascade of Ca(2+) release from the ER store. To test these blockers in vivo, in a rat renal I/R model, pretreatment with nicardipine and TMB-8, but not dantrolene, can protect renal function. Taken together, our results suggest that after I/R injury, Ca(2+) influx through the L-type calcium channel triggers the Ca(2+) release from the InsP3R and finally induces apoptosis. The InsP3R could be a new target for the treatment of renal I/R injury.
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Authors | Di Wu, Xiangmei Chen, Rui Ding, Xi Qiao, Suozhu Shi, Yuansheng Xie, Quan Hong, Zhe Feng |
Journal | American journal of nephrology
(Am J Nephrol)
Vol. 28
Issue 3
Pg. 487-99
( 2008)
ISSN: 1421-9670 [Electronic] Switzerland |
PMID | 18185015
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2008 S. Karger AG, Basel. |
Chemical References |
- Calcium Channel Blockers
- Calcium Channels, L-Type
- Inositol 1,4,5-Trisphosphate Receptors
- Muscle Relaxants, Central
- Ryanodine Receptor Calcium Release Channel
- Malondialdehyde
- Antimycin A
- Cytochromes c
- Superoxide Dismutase
- Dantrolene
- Calcium
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Topics |
- Animals
- Antimycin A
- Apoptosis
(drug effects)
- Blood Pressure
(drug effects)
- Calcium
(metabolism)
- Calcium Channel Blockers
- Calcium Channels, L-Type
(metabolism)
- Cells, Cultured
- Cytochromes c
(metabolism)
- DNA Fragmentation
(drug effects)
- Dantrolene
- Endoplasmic Reticulum
(metabolism)
- Epithelial Cells
(metabolism)
- Inositol 1,4,5-Trisphosphate Receptors
(antagonists & inhibitors, metabolism)
- Kidney Tubules, Proximal
(metabolism, pathology)
- Male
- Malondialdehyde
(metabolism)
- Muscle Relaxants, Central
- Rats
- Rats, Wistar
- Reperfusion Injury
(enzymology, metabolism, pathology)
- Ryanodine Receptor Calcium Release Channel
(metabolism)
- Superoxide Dismutase
(metabolism)
- Urothelium
(metabolism)
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