Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells.
Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells.
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使用 MITO-Porter 线粒体递送 bongkrekic 酸可防止人 HeLa 细胞凋亡的诱导。
DOI：
10.1002/jps.23442
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Harashima H.
中科院分区：
文献类型：
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作者：
Yamada Y;Nakamura K;Furukawa R;Kawamura E;Moriwaki T;Matsumoto K;Okuda K;Shindo M;Harashima H.
线粒体功能障碍与多种人类疾病有关，这一事实表明线粒体功能障碍有望成为这些疾病的靶细胞器。Bongkrekic acid(BKA)是一种作为腺核苷酸转运体配体的化学物质，已知能有效地抑制与细胞凋亡相关的线粒体通透性转变。因此，将其输送到线粒体将是治疗线粒体疾病的创新疗法，线粒体疾病在很大程度上与细胞凋亡有关。在这里，我们报告了Mito-Porter，一种通过线粒体膜融合传递线粒体的创新纳米载体，用于将BKA传递到线粒体。我们首先构建了BKA-Mito-Porter，其中BKA被包含在Mito-Porter的脂膜中。然后我们证实，BKA-Mito-Porter与传统的Mito-Porter类似，可以有效地内化到细胞中，并被运送到线粒体。此外，我们还通过检测caspase3/7活性来评价BKA-Mito-Porter在HeLa细胞中的抗凋亡作用。结果证实，BKA-Mito-Porter与裸BKA相比具有较强的抗细胞凋亡作用。这里报道的结果证明了它作为线粒体医学候选药物在针对线粒体疾病的治疗中的应用潜力。©2013威利期刊公司和美国药剂师协会药学杂志102：1008-1015,2013
The fact that mitochondrial dysfunction has been implicated in a variety of human diseases suggests that they would be expected as a target organelle for these diseases. Bongkrekic acid (BKA) is a chemical that functions as a ligand of the adenine nucleotide translocator and is known to potently inhibit the mitochondrial permeability transition that is associated with apoptosis. Thus, delivering it to mitochondria would be an innovative therapy for the treatment of mitochondrial diseases that are largely associated with apoptosis. Here, we report on the use of a MITO-Porter, an innovative nanocarrier for mitochondrial delivery via mitochondrial membrane fusion, for delivering BKA to mitochondria. We first constructed a BKA-MITO-Porter, in which BKA is contained in lipid envelopes of a MITO-Porter. We then confirmed that the BKA–MITO-Porter was efficiently internalized into cells and is delivered to mitochondria, similar to a conventional MITO-Porter. Moreover, we evaluated the antiapoptosis effect of the BKA–MITO-Porter in HeLa cells by measuring caspase 3/7 activity. The findings confirmed that the BKA–MITO-Porter showed a strong antiapoptosis effect compared with naked BKA. The results reported here demonstrate its potential for the use in therapies aimed at mitochondrial diseases, as a mitochondrial medicine candidate. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1008–1015, 2013