Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8A beta cell death
Involvement of Ca2+-mediated apoptotic signals in palmitate-induced MIN6N8A beta cell death
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DOI：
10.1016/j.mce.2007.04.004
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发表时间：
2007-06-30
影响因子：
4.1
通讯作者：
Yup, Kang
中科院分区：
文献类型：
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作者：
Sung-E., Choi;Hyo-Eun, Kim;Yup, Kang
细胞外钙离子螯合剂EGTA和L-型钙离子通道阻断剂硝苯地平和尼莫地平对棕榈酸诱导的MIN 6 N8 a β细胞凋亡具有保护作用，而钙离子通道开放剂Bay K8644则增强了凋亡过程。此外，磷酸化形式的坏，结合磷酸化Akt，减少响应棕榈酸和棕榈酸诱导的Akt和坏的脱磷酸化依赖于Ca-2+流入。瞬时表达具有催化活性的Akt阻止了棕榈酸诱导的MIN 6 N8 a细胞凋亡。溴氰菊酯，钙激活磷酸酶的抑制剂，延迟Akt和Bad去磷酸化，然后保护MIN 6 N8 a细胞免受棕榈酸诱导的凋亡。另一方面，棕榈酸酯被发现诱导CHOP，一个凋亡的转录因子，在响应ER应激，这种诱导增强的Ca 2+内流。我们的研究表明，Ca 2+内流和随后的Ca 2+介导的凋亡信号参与棕榈酸诱导的β细胞死亡。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
The extracellular Ca2+ chelator EGTA and L-type Ca2+ channel blockers, such as, nifedipine and nimodipine were found to have a protective effect on palmitate-induced MIN6N8a beta cell apoptosis, whereas the Ca2+ channel opener, Bay K8644, enhanced the apoptotic process. Moreover, the phospho-form of Bad, in conjunction with phospho-Akt, was reduced in response to palmitate and the palmitate-induced dephosphorylations of Akt and Bad were dependent on Ca-2+ influx. The transient expression of catalytically active Akt prevented MIN6N8a cells from palmitate-induced apoptosis. Deltamethrin, an inhibitor of Ca2+-activated phosphatase, delayed Akt and Bad dephosphorylations, and then protected MIN6N8a cells from palmitate-induced apoptosis. On the other hand, palmitate was found to induce CHOP, an apoptotic transcription factor in response to ER stress, and this induction was enhanced by Ca2+ influx. Our studies suggested that Ca2+ influx and subsequent Ca2+-mediated apoptotic signals are involved in palmitate-induced beta cell death. (C) 2007 Elsevier Ireland Ltd. All rights reserved.