Boquist L
Diabetologia. 1984 Sep;27(3):379-86. doi: 10.1007/BF00304854.
Isolated mouse liver mitochondria incubated with alloxan showed stimulated resting (state 4) respiration with succinate, and inhibited resting respiration with pyridine-linked substrates, whereas active (state 3) respiration was decreased with both kinds of substrates. The effects were dependent on the concentration of alloxan, on the energy state, and on transport of inorganic phosphate and uptake of Ca2+. Using succinate as substrate, the effects of alloxan on endogenous Mg2+, K+ and adenine nucleotides, uptake of K+, accumulated Ca2+, membrane potential and volume were studied in liver mitochondria, and in addition efflux of endogenous K+ and accumulated Ca2+ were investigated in mouse islet mitochondria. High concentrations of alloxan (greater than or equal to 3 mmol/l) induced efflux of endogenous Mg2+, K+ and adenine nucleotides, efflux of accumulated Ca2+, inhibition of uptake of K+, loss of membrane potential, and swelling. Low concentrations of alloxan (less than 3 mmol/l) had similar effects only in the presence of added Ca2+ and inorganic phosphate. The influence of potentially protective agents was studied mainly with regard to alloxan induced swelling. Complete or partial protection was offered by antimycin A, malonate, La3+, Ni2+, ruthenium red, mersalyl and N-ethylmaleimide, suggesting requirement for energized transport of Ca2+ and uptake of inorganic phosphate. The start of the respiratory changes, decrease of membrane potential and loss of Mg2+ preceded the release of accumulated Ca2+, which occurred in parallel with efflux of K+ and swelling. The loss of Ca2+ in association with swelling agrees with data previously obtained using qualitative and quantitative electron microscopy and X-ray microanalysis of islet beta cells from alloxan-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
用四氧嘧啶孵育分离的小鼠肝脏线粒体，结果显示其琥珀酸介导的静息（状态4）呼吸增强，而吡啶连接底物介导的静息呼吸受到抑制，同时两种底物介导的活性（状态3）呼吸均减弱。这些效应取决于四氧嘧啶的浓度、能量状态以及无机磷酸的转运和钙离子的摄取。以琥珀酸为底物，研究了四氧嘧啶对肝脏线粒体中内源性镁离子、钾离子和腺嘌呤核苷酸、钾离子摄取、累积钙离子、膜电位和体积的影响，此外还研究了小鼠胰岛线粒体中内源性钾离子和累积钙离子的外流。高浓度的四氧嘧啶（大于或等于3 mmol/L）可诱导内源性镁离子、钾离子和腺嘌呤核苷酸外流、累积钙离子外流、钾离子摄取受抑制、膜电位丧失以及肿胀。低浓度的四氧嘧啶（小于3 mmol/L）仅在添加钙离子和无机磷酸的情况下具有类似效应。主要针对四氧嘧啶诱导的肿胀研究了潜在保护剂的影响。抗霉素A、丙二酸、镧离子、镍离子、钌红、汞撒利和N - 乙基马来酰胺可提供完全或部分保护，这表明钙离子的能量驱动转运和无机磷酸的摄取是必需的。呼吸变化的起始、膜电位的降低和镁离子的丧失先于累积钙离子的释放，而累积钙离子的释放与钾离子外流和肿胀同时发生。钙离子丧失与肿胀相关，这与先前使用定性和定量电子显微镜以及对四氧嘧啶处理小鼠的胰岛β细胞进行X射线微分析所获得的数据一致。（摘要截短于250字）
