Lacidipine attenuates TNF-α-induced cardiomyocyte apoptosis

•Lacidipine protects cardiomyocyte against apoptosis induced by TNF-α.•Lacidipine reduces TNF-α-induced apoptosis via blocking caspase-12, 3 successively.•Lacidipine alleviates endoplasmic reticulum stress by down-regulating CRT expression.•ERS-mediated pathway is involved in the mechanism of TNF-α-...

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Veröffentlicht in:Cytokine (Philadelphia, Pa.) Pa.), 2015-01, Vol.71 (1), p.60-65
Hauptverfasser: Wang, Qiu-Lin, Zhao, Lei, Feng, Na, Zhou, Peng, Wu, Qi, Fan, Rong, Li, Juan, Zhang, Shu-Miao, Wang, Yue-Min, Xu, Xue-Zeng, Yu, Shi-Qiang, Yi, Ding-Hua, Pei, Jian-Ming
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Sprache:eng
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Zusammenfassung:•Lacidipine protects cardiomyocyte against apoptosis induced by TNF-α.•Lacidipine reduces TNF-α-induced apoptosis via blocking caspase-12, 3 successively.•Lacidipine alleviates endoplasmic reticulum stress by down-regulating CRT expression.•ERS-mediated pathway is involved in the mechanism of TNF-α-induced apoptosis. This study was designed to investigate whether lacidipine elicited a protective role on cardiomyocyte against apoptosis induced by TNF-α. Neonatal rat cardiomyocytes were randomly assigned into different groups. TUNEL staining was utilized to detect apoptosis, and caspase-3 and caspse-12 were determined. To explore the underlying mechanism, Z-ATAD-FMK (a selective caspase-12 inhibitor) was used to identify the key molecule involved. TNF-α increased caspase-3 expression, which was mediated by increased caspase-12 expression. In the meantime, apoptosis was significantly induced by TNF-α. Lacidipine lowered caspase-12 and caspase-3 expression, and cardiomyocyte apoptosis induced by TNF-α. The results suggest that lacidipine attenuates TNF-α -induced apoptosis via inhibition of caspase-12 and caspase-3 successively.
ISSN:1043-4666
1096-0023
DOI:10.1016/j.cyto.2014.08.004