caa a22 4500 39755530X CHVBK 20180308164800.0 cr unu---uuuuu 161202e199602 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021235 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021235 Uncoupling Mechanism of Glycoside Antibiotic Aculeximycin in Isolated Rat-Liver Mitochondria [Elektronische Daten] [Hideto Miyoshi, Motohito Tamaki, Hideaki Murata, Takaya Ikemoto, Toshiro Shibuya, Ken-ichi Harada, Makoto Suzuki, Hajime Iwamura] Effects of basic glycoside antibiotic aculeximycin (ACM) on the oxidative phosphorylation of rat-liver mitochondria were examined. ACM was shown to be a potent uncoupler of the oxidative phosphorylation. To cause the same extent of respiration release, higher concentration of ACM was required in phosphate (P1)-free medium than in P1 medium. During the uncoupling caused by ACM in P1 medium, large amplitude swelling and oxidation of intramitochondrial NAD(P)H occurred, indicating that ACM remarkably enhances permeability of the inner mitochondrial membrane. The P1 uptake via P1/H+ symporter was shown to play an important, but not essential, role in the uncoupling by ACM, indicating the increase in membrane permeability is mostly due to acceleration of P1/H+ influx through P1/H+symporter activated by ACM. ACM is the first naturally occurring antibiotic, to our knowledge, which activates P1/H+ symporter. However, since the inhibition of P1/H+ symporter by N-ethylmaleimide did not completely abolish the uncoupling activity of ACM, and ACM induced the uncoupling even in P1-free medium, an increase in the membrane permeability for other ions, such as Na+ and K+, due to a different action mechanism has also to be considered. On the other hand, positively charged amine local anesthetics, like dibucaine, prevented the uncoupling activity by ACM in both P1 and P1, -free medium. The uncoupling activity of iV-diacetylated ACM lacking free ami no groups was ca. l/12Oth that of ACM, indicating that positively charged amino groups are important for the uncoupling activity. It is suggested that some specific interactions between positively charged amino groups of ACM and the binding site, which is probably negatively charged, are triggers that affect the permeability of the inner mitochondrial membrane. Amine local anesthetics may mask the negative charge of the binding site, thereby interfering with ACM binding. © by the Journal of Biochemistry Regular Papers nationallicence antibiotic (aculeximycin) nationallicence mitochondria (rat-liver) nationallicence oxidative phosphorylation nationallicence uncoupling nationallicence Miyoshi Hideto Department of Agricultural Chemistry, Kyoto University Sakyo-ku, Kyoto 606 aut Tamaki Motohito Department of Agricultural Chemistry, Kyoto University Sakyo-ku, Kyoto 606 aut Murata Hideaki Faculty of Pharmacy, Meijo University Tempaku, Nagoya 468 aut Ikemoto Takaya Teikyo University School of Medicine 2-11-1 Kaga, Itabashi-ku, Tokyo 173 aut Shibuya Toshiro Teikyo University School of Medicine 2-11-1 Kaga, Itabashi-ku, Tokyo 173 aut Harada Ken-ichi Faculty of Pharmacy, Meijo University Tempaku, Nagoya 468 aut Suzuki Makoto Faculty of Pharmacy, Meijo University Tempaku, Nagoya 468 aut Iwamura Hajime Department of Agricultural Chemistry, Kyoto University Sakyo-ku, Kyoto 606 aut The Journal of Biochemistry Oxford University Press 119/2(1996-02), 274-280 0021-924X 119:2<274 1996 119 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021235 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021235 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Miyoshi Hideto Department of Agricultural Chemistry, Kyoto University Sakyo-ku, Kyoto 606 aut NATIONALLICENCE 700 1- Tamaki Motohito Department of Agricultural Chemistry, Kyoto University Sakyo-ku, Kyoto 606 aut NATIONALLICENCE 700 1- Murata Hideaki Faculty of Pharmacy, Meijo University Tempaku, Nagoya 468 aut NATIONALLICENCE 700 1- Ikemoto Takaya Teikyo University School of Medicine 2-11-1 Kaga, Itabashi-ku, Tokyo 173 aut NATIONALLICENCE 700 1- Shibuya Toshiro Teikyo University School of Medicine 2-11-1 Kaga, Itabashi-ku, Tokyo 173 aut NATIONALLICENCE 700 1- Harada Ken-ichi Faculty of Pharmacy, Meijo University Tempaku, Nagoya 468 aut NATIONALLICENCE 700 1- Suzuki Makoto Faculty of Pharmacy, Meijo University Tempaku, Nagoya 468 aut NATIONALLICENCE 700 1- Iwamura Hajime Department of Agricultural Chemistry, Kyoto University Sakyo-ku, Kyoto 606 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 119/2(1996-02), 274-280 0021-924X 119:2<274 1996 119 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford