BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore
BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore
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DOI：
10.1128/mcb.22.6.1926-1935.2002
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发表时间：
2002-03-01
影响因子：
5.3
通讯作者：
Bernardi, P
中科院分区：
文献类型：
--
作者：
Risso, A;Braidot, E;Bernardi, P
BMAP-28是放线菌素家族的一种牛抗菌肽，可诱导人肿瘤细胞系和激活的人淋巴细胞膜通透性和死亡，但不能诱导静止的人淋巴细胞。此外，我们还发现BMAP-28导致单个细胞和分离的线粒体内线粒体膜的去极化。这种作用与Ca~(2+)有协同作用，并被环孢素A抑制，提示去极化依赖于线粒体通透性转换孔的开放。根据线粒体对钙黄素的通透性和细胞色素c的释放，研究了通透性转变的发生。我们发现BMAP-28以一种对环孢素敏感的方式使线粒体渗透到包裹钙黄绿素的线粒体中，并在原位释放细胞色素c。我们的结果表明，BMAP-28是线粒体通透性转换孔的诱导剂，其细胞毒作用取决于其对线粒体通透性的影响。
BMAP-28, a bovine antimicrobial peptide of the cathelicidin family, induces membrane permeabilization and death in human tumor cell lines and in activated, but not resting, human lymphocytes. In addition, we found that BMAP-28 causes depolarization of the inner mitochondrial membrane in single cells and in isolated mitochondria. The effect of the peptide was synergistic with that of Ca2+ and inhibited by cyclosporine, suggesting that depolarization depends on opening of the mitochondrial permeability transition pore. The occurrence of a permeability transition was investigated on the basis of mitochondrial permeabilization to calcein and cytochrome c release. We show that BMAP-28 permeabilizes mitochondria to entrapped calcein in a cyclosporine-sensitive manner and that it releases cytochrome c in situ. Our results demonstrate that BMAP-28 is an inducer of the mitochondrial permeability transition pore and that its cytotoxic potential depends on its effects on mitochondrial permeability.