| RRC ID |
44238
|
| 著者 |
Yamada Y, Nakamura K, Furukawa R, Kawamura E, Moriwaki T, Matsumoto K, Okuda K, Shindo M, Harashima H.
|
| タイトル |
Mitochondrial delivery of bongkrekic acid using a MITO-Porter prevents the induction of apoptosis in human HeLa cells.
|
| ジャーナル |
J Pharm Sci
|
| Abstract |
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.
|
| 巻・号 |
102(3)
|
| ページ |
1008-15
|
| 公開日 |
2013-3-1
|
| DOI |
10.1002/jps.23442
|
| PII |
S0022-3549(15)31186-2
|
| PMID |
23315986
|
| MeSH |
Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / pharmacology
Apoptosis / drug effects*
Bongkrekic Acid / administration & dosage*
Bongkrekic Acid / pharmacology
Drug Delivery Systems*
HeLa Cells
Humans
Liposomes / chemistry*
Liposomes / metabolism
Mitochondria / drug effects
Mitochondria / metabolism*
|
| IF |
2.997
|
| 引用数 |
17
|
|
WOS 分野
|
CHEMISTRY, MEDICINAL
PHARMACOLOGY & PHARMACY
CHEMISTRY, MULTIDISCIPLINARY
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa |
