Moore G A, McConkey D J, Kass G E, O'Brien P J, Orrenius S
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
FEBS Lett. 1987 Nov 30;224(2):331-6. doi: 10.1016/0014-5793(87)80479-9.
Treatment of rat liver microsomes with 2,5-di(tert-butyl)-1,4-benzohydroquinone caused a dose-related inhibition (Ki congruent to 1 microM) of ATP-dependent Ca2+ sequestration. This was paralleled by a similar impairment of the microsomal Ca2+-stimulated ATPase activity. In contrast, the hydroquinose failed to induce Ca2+ release from Ca2+-loaded liver mitochondria (supplied with ATP), and inhibited neither the mitochondrial F1F0-ATPase nor the Ca2+-stimulated ATPase activity of the hepatic plasma membrane fraction. The inhibition of microsomal Ca2+ sequestration was not associated with any apparent alteration of membrane permeability or loss of other microsomal enzyme activities or modification of microsomal protein thiols. These findings suggest that 2,5-di(tert-butyl)-1,4-benzohydroquinone is a potent and selective inhibitor of liver microsomal Ca2+ sequestration which may be a useful tool in studies of Ca2+ fluxes in intact cells and tissues.
用2,5 - 二(叔丁基)-1,4 - 苯二酚处理大鼠肝微粒体,会导致ATP依赖的Ca2+ 螯合作用出现剂量相关的抑制(Ki约为1 microM)。这与微粒体Ca2+ 刺激的ATP酶活性受到类似损害是平行的。相比之下,对苯二酚未能诱导Ca2+ 从加载了Ca2+ 的肝线粒体(供应有ATP)中释放,并且既不抑制线粒体F1F0 - ATP酶,也不抑制肝细胞膜部分的Ca2+ 刺激的ATP酶活性。微粒体Ca2+ 螯合作用的抑制与膜通透性的任何明显改变、其他微粒体酶活性的丧失或微粒体蛋白硫醇的修饰均无关。这些发现表明,2,5 - 二(叔丁基)-1,4 - 苯二酚是肝微粒体Ca2+ 螯合作用的一种有效且选择性的抑制剂,这可能是完整细胞和组织中Ca2+ 通量研究的一种有用工具。