Abramson J J, Cronin J R, Salama G
Department of Physics, Portland State University, Oregon 97207.
Arch Biochem Biophys. 1988 Jun;263(2):245-55. doi: 10.1016/0003-9861(88)90633-9.
The copper containing phthalocyanine dyes, alcian blue, copper phthalocyanine tetrasulfonic acid, and Luxol fast blue MBSN are found to induce rapid calcium efflux from actively loaded sarcoplasmic reticulum (SR) vesicles. Alcian blue (5 microM), with 1 mM free Mg2+ triggered Ca2+ efflux at rates greater than 20 nmol/mg of SR/s. As in the case of Ca2+ efflux induced by calcium, heavy metals, or SH oxidation with Cu2+/cysteine, efflux induced by phthalocyanines is also stimulated by adenine containing nucleotides and inhibited by millimolar Mg2+ and submicromolar ruthenium red (RR). In addition, analogs of RR, such as hexamminecobalt(III) chloride or hexammineruthenium(III) chloride also inhibit Ca2+ efflux but are effective at somewhat higher concentrations (approximately 50 microM). Calcium release stimulated by phthalocyanines is specific for SR derived from the terminal cisternae region rather than longitudinal SR. Preincubation of alcian blue with the reducing agents, sodium dithionite, dithiothreitol, or cysteine causes complete loss of Ca2+ release activity from SR vesicles. Reoxidation of the alcian blue leads to return of the Ca2+ release activity of the phthalocyanine dye. The copper containing phthalocyanine dyes appear to cause rapid Ca2+ release from SR vesicles by oxidizing sulfhydryl groups associated with the calcium release channel. Moreover, phthalocyanines appear to act by oxidizing a pair of neighboring sulfhydryls to a disulfide because subsequent additions of the reducing agent dithiothreitol promote the closure of the Ca2+ channel and calcium re-uptake.
已发现含铜的酞菁染料、阿尔新蓝、酞菁四磺酸铜和卢克斯奥尔坚牢蓝MBSN可诱导主动加载的肌浆网（SR）囊泡快速释放钙。在含有1 mM游离Mg2+的情况下，5 microM的阿尔新蓝引发的Ca2+释放速率大于20 nmol/mg SR/s。与钙、重金属或Cu2+/半胱氨酸引发的SH氧化所诱导的Ca2+释放情况一样，酞菁诱导的释放也受到含腺嘌呤核苷酸的刺激，并受到毫摩尔浓度的Mg2+和亚微摩尔浓度的钌红（RR）的抑制。此外，RR的类似物，如氯化六氨合钴（III）或氯化六氨合钌（III）也抑制Ca2+释放，但在略高的浓度（约50 microM）下才有效。酞菁刺激的钙释放对源自终池区域而非纵向SR的SR具有特异性。用还原剂连二亚硫酸钠、二硫苏糖醇或半胱氨酸对阿尔新蓝进行预孵育会导致SR囊泡的Ca2+释放活性完全丧失。阿尔新蓝的再氧化会导致酞菁染料的Ca2+释放活性恢复。含铜的酞菁染料似乎通过氧化与钙释放通道相关的巯基来导致SR囊泡快速释放Ca2+。此外，酞菁似乎是通过将一对相邻的巯基氧化为二硫键来起作用的，因为随后添加还原剂二硫苏糖醇会促进Ca2+通道的关闭和钙的重新摄取。
