Iron deprivation induces apoptosis via mitochondrial changes related to Bax translocation
Iron deprivation induces apoptosis via mitochondrial changes related to Bax translocation
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DOI：
10.1007/s10495-005-0812-8
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发表时间：
2005-03-01
期刊：
影响因子：
7.2
通讯作者：
Kovár, J
中科院分区：
文献类型：
--
作者：
Koc, M;Nad'ová, Z;Kovár, J
为了阐明铁剥夺诱导细胞凋亡的机制，我们比较了对铁剥夺诱导的细胞凋亡敏感的细胞（38C13）和抵抗的细胞（EL4）。通过在限定的无铁培养基中孵育来实现铁剥夺。我们检测到caspase-3的激活，以及caspase-9的激活在敏感的细胞，而不是在铁剥夺下的抗性细胞。铁剥夺导致细胞色素c从线粒体释放到细胞质中，只有在敏感的细胞，但它不影响细胞质定位的Apaf-1在敏感和耐药细胞。由于铁剥夺，敏感细胞的线粒体膜电位（Δ psi（m））在24 h内消失。抗凋亡Bcl-2蛋白被发现与敏感和耐药细胞的线粒体和协会没有改变铁剥夺。另一方面，铁剥夺下，我们检测到易位的促凋亡Bax蛋白从细胞质线粒体的敏感细胞，但在耐药细胞。两者合计，我们认为，铁剥夺诱导细胞凋亡通过线粒体的变化有关促凋亡Bax易位到线粒体，线粒体膜电位的崩溃，释放细胞色素c从线粒体，和激活caspase-9和caspase-3。
In order to elucidate the mechanisms involved in apoptosis induction by iron deprivation, we compared cells sensitive (38C13) and resistant (EL4) to apoptosis induced by iron deprivation. Iron deprivation was achieved by incubation in a defined iron-free medium. We detected the activation of caspase-3 as well as the activation of caspase-9 in sensitive cells but not in resistant cells under iron deprivation. Iron deprivation led to the release of cytochrome c from mitochondria into the cytosol only in sensitive cells but it did not affect the cytosolic localization of Apaf-1 in both sensitive and resistant cells. The mitochondrial membrane potential (Delta psi(m)) was dissipated within 24 h in sensitive cells due to iron deprivation. The antiapoptotic Bcl-2 protein was found to be associated with mitochondria in both sensitive and resistant cells and the association did not change under iron deprivation. On the other hand, under iron deprivation we detected translocation of the proapoptotic Bax protein from the cytosol to mitochondria in sensitive cells but not in resistant cells. Taken together, we suggest that iron deprivation induces apoptosis via mitochondrial changes concerning proapoptotic Bax translocation to mitochondria, collapse of the mitochondrial membrane potential, release of cytochrome c from mitochondria, and activation of caspase-9 and caspase-3.