Mitochondrial permeability transition induced DNA-fragmentation in the rat hippocampus following hypoglycemia

被引:48
作者
Ferrand-Drake, M [1 ]
Friberg, H [1 ]
Wieloch, T [1 ]
机构
[1] Univ Lund Hosp, Wallenberg Neurosci Ctr, Expt Brain Res Lab, S-22185 Lund, Sweden
关键词
neuronal death; hypoglycemia; DNA fragmentation; mitochondria; mitochondrial permeability transition;
D O I
10.1016/S0306-4522(98)00559-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In the present study the time-course of DNA fragmentation following insulin-induced hypoglycemia was examined. In situ localization of DNA breaks were studied by the terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labelling method, and the temporal profile of DNA-fragmentation by agarose gel electrophoresis. Cell nuclei displayed terminal deoxynucleotidyl transferase-deoxyuridine triphosphate nick-end labelling within 3 h of recovery following 30 min of a hypoglycemic insult, and DNA from the hippocampus displayed oligonucleosomal fragmentation. Ultrastructural examination of the dentate granule cells showed mitochondrial swelling during the acute phase of the hypoglycemic insult, which preceded the DNA fragmentation seen in the recovery phase. Cyclosporin A but not tacrolimus, prevented mitochondrial swelling and subsequent DNA fragmentation. We conclude that during severe energy deprivation following hypoglycemia, mitochondrial swelling occurs due to mitochondrial permeability transition and I:hat factors are released, which upon recovery can activate processes leading to DNA fragmentation and cell death. (C) 1999 IBRO. Published by Elsevier Science Ltd.
引用
收藏
页码:1325 / 1338
页数:14
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