首页> 外文期刊>American Journal of Physiology >Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of mIMCD3 cells.
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Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of mIMCD3 cells.

机译:线粒体功能障碍是高NaCl诱导的mIMCD3细胞凋亡的早期事件。

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Raising osmolality to 700 mosmol/kgH(2)O by the addition of NaCl rapidly kills most murine inner renal medullary collecting duct cells (mIMCD3), but they survive at 500 mosmol/kgH(2)O. At 300 and 500 mosmol/kgH(2)O, NADH autofluorescence is present in a mitochondria-associated, punctate perinuclear pattern. Within 45 s to 30 min at 700 mosmol/kgH(2)O, the autofluorescence spreads diffusely throughout the cell. This correlates with mitochondrial membrane depolarization, measured as decreased tetramethylrhodamine methyl ester perchlorate (TMRM) fluorescence. Mitochondrial dysfunction should increase the cellular ADP/ATP ratio. In agreement, this ratio increases within 1-6 h. Mitochondrial morphology (transmission electron microscopy) is unaffected, but nuclear hypercondensation becomes evident. Progressive apoptosis occurs beginning 1 h after osmolality is raised to 700, but not to 500, mosmol/kgH(2)O. General caspase activity and caspase-9 activity increase only after 6 h at 700 mosmol/kgH(2)O. The mitochondrial Bcl-2/Bax ratio decreases within 1-3 h, but no cytochrome c release is evident. The mitochondria contain little p53 at any osmolality. Adding urea to 700 mosmol/kgH(2)O does not change NADH or TMRM fluorescence. We conclude that extreme acute hypertonicity causes a mitochondrial dysfunction involved in the initiation of apoptosis.
机译:通过添加NaCl将重量克分子渗透压升高至700 mosmol / kgH(2)O,可迅速杀死大多数鼠内肾髓质收集导管细胞(mIMCD3),但它们在500 mosmol / kgH(2)O下存活。在300和500 mosmol / kgH(2)O时,NADH自发荧光以线粒体相关的点状核周模式存在。在700 mosmol / kgH(2)O下45到30分钟内,自发荧光在整个细胞中扩散。这与线粒体膜去极化有关,以减少的四甲基罗丹明甲酯高氯酸盐(TMRM)荧光表示。线粒体功能障碍应增加细胞的ADP / ATP比。一致地,该比率在1-6小时内增加。线粒体形态(透射电子显微镜)不受影响,但核超凝变得明显。渗透压升至渗透压升至700 mosmol / kgH(2)O的1小时后,开始发生凋亡。一般caspase活性和caspase-9活性仅在700 mosmol / kgH(2)O下6小时后才增加。线粒体Bcl-2 / Bax比值在1-3小时内下降,但没有明显的细胞色素c释放。线粒体在任何摩尔渗透压浓度下都几乎不含p53。将尿素添加到700 mosmol / kgH(2)O中不会改变NADH或TMRM荧光。我们得出的结论是,极端急性高渗性会导致细胞凋亡引发线粒体功能障碍。

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