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

M Ferrand-Drake, H Friberg, T Wieloch - Neuroscience, 1999 - Elsevier
M Ferrand-Drake, H Friberg, T Wieloch
Neuroscience, 1999Elsevier
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 3h of recovery following 30min of a hypoglycemic insult, and DNA from the …
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 3h of recovery following 30min 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 that factors are released, which upon recovery can activate processes leading to DNA fragmentation and cell death.
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