Doxorubicin directly binds to the cardiac-type ryanodine receptor

被引：51

作者：

Saeki, K

Obi, I

Ogiku, N

Shigekawa, M

Imagawa, T

Matsumoto, T

机构：

[1] Tanabe Seiyaku Co Ltd, Discovery Res Lab, Toda, Saitama 3358505, Japan

[2] Natl Cardiovasc Ctr, Inst Res, Dept Mol Physiol, Suita, Osaka 5658565, Japan

[3] Hokkaido Univ, Div Chem, Biochem Grad Sch Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan

来源：

LIFE SCIENCES | 2002年 / 70卷 / 20期

关键词：

doxorubicin; ryanodine receptor; binding; caffeine;

D O I：

10.1016/S0024-3205(02)01524-2

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：

The clinical use of doxorubicin, an antineoplasmic agent, is limited by its extensive cardiotoxicity which is mediated by the mobilization of intracellular Ca2+ from SR. In order to elucidate the mechanism of Ca2+ release, we analyzed the binding sites of doxorubicin on rabbit cardiac SR (sarcoplasmic reticulum). One of the binding sites was identified as cardiac-type ryanodine receptor (RyR2) which was purified by immunoprecipitation from solubilized cardiac SR in the presence of DTT. Ligand blot analysis revealed the direct binding of doxorubicin to RyR2. The binding of doxorubicin to RyR2 was specific and displaced by caffeine. Both doxorubicin and caffeine enhanced [H-3]-ryanodine binding to RyR2 in a Ca2+ dependent manner. These results suggest that there is a doxorubicin binding site on RyR2. (C) 2002 Elsevier Science Inc. All rights reserved.

引用

页码：2377 / 2389

页数：13

共 25 条

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