Design of manganese porphyrin modified with mitochondrial signal peptide for a new antioxidant

被引:48
作者
Asayama, Shoichiro [1 ]
Kawamura, Eri [1 ]
Nagaoka, Shoji [1 ]
Kawakami, Hiroyoshi [1 ]
机构
[1] Tokyo Metropolitan Univ, Dept Appl Chem, Tokyo 1920397, Japan
基金
日本学术振兴会;
关键词
water-soluble manganese porphyrin; superoxide dismutase activity; signal peptide; mitochondrion; organella targeting;
D O I
10.1021/mp0500667
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
A new design of antioxidant, consisting of manganese (Mn) porphyrin and signal peptide for mitochondrial targeting, is reported. The resulting Mn-porphyrin-oligopeptide conjugate exhibited significant superoxide dismutase (SOD) activity and decomposed peroxynitrite (ONOO-). The new antioxidant caused the swelling of isolated mitochondria. By using the pH-sensitive drug carrier for intracellular delivery, furthermore, the new conjugate recovered the viability of lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. These results suggest that the Mn-porphyrin modified with signal peptide for mitochondrial targeting is promising for a new class of antioxidants.
引用
收藏
页码:468 / 470
页数:3
相关论文
共 15 条
[1]   Poly(L-histidine) with several aminoethyl groups for a new pH-sensitive DNA carrier [J].
Asayama, S ;
Sekine, T ;
Hamaya, A ;
Kawakami, H ;
Nagaoka, S .
POLYMERS FOR ADVANCED TECHNOLOGIES, 2005, 16 (07) :567-570
[2]   Design of metalloporphyrin-carbohydrate conjugates for a new superoxide dismutase mimic with cellular recognition [J].
Asayama, S ;
Mizushima, K ;
Nagaoka, S ;
Kawakami, H .
BIOCONJUGATE CHEMISTRY, 2004, 15 (06) :1360-1363
[3]   Chemical modification of manganese porphyrins with biomolecules for new functional antioxidants [J].
Asayama, S ;
Mori, T ;
Nagaoka, S ;
Kawakami, H .
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 2003, 14 (11) :1169-1179
[4]   Facile chemical modification of the poly(L-histidine) for a new pH-sensitive polypeptide [J].
Asayama, S ;
Kawakami, H ;
Nagaoka, S .
CHEMISTRY LETTERS, 2003, 32 (12) :1152-1153
[5]   Nitric oxide and its role in apoptosis [J].
Brüne, B ;
von Knethen, A ;
Sandau, KB .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1998, 351 (03) :261-272
[6]   Selective targeting of synthetic antioxidants to mitochondria: towards a mitochondrial medicine for neurodegenerative diseases? [J].
Dessolin, J ;
Schuler, M ;
Quinart, A ;
De Giorgi, F ;
Ghosez, L ;
Ichas, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 447 (2-3) :155-161
[7]  
Kawakami H, 1999, POLYM ADVAN TECHNOL, V10, P270, DOI 10.1002/(SICI)1099-1581(199905)10:5<270::AID-PAT873>3.0.CO
[8]  
2-C
[9]   Mitochondrial precursor signal peptide induces a unique permeability transition and release of cytochrome c from liver and brain mitochondria [J].
Kushnareva, YE ;
Polster, BM ;
Sokolove, PM ;
Kinnally, KW ;
Fiskum, G .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2001, 386 (02) :251-260
[10]   Effect of leader peptides on the permeability of mitochondria [J].
Lu, Y ;
Beavis, AD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) :13555-13561