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

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Mitochondrial permeability transition induced DNA-fragmentation in the rat hippocampus following hypoglycemia. / Ferrand-Drake, M.; Friberg, H.; Wieloch, T.

I: Neuroscience, Vol. 90, Nr. 4, 01.06.1999, s. 1325-1338.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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T1 - Mitochondrial permeability transition induced DNA-fragmentation in the rat hippocampus following hypoglycemia

AU - Ferrand-Drake, M.

AU - Friberg, H.

AU - Wieloch, T.

PY - 1999/6/1

Y1 - 1999/6/1

N2 - 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 that factors are released, which upon recovery can activate processes leading to DNA fragmentation and cell death.

AB - 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 that factors are released, which upon recovery can activate processes leading to DNA fragmentation and cell death.

KW - DNA fragmentation

KW - Hypoglycemia

KW - Mitochondria

KW - Mitochondrial permeability transition

KW - Neuronal death

UR - http://www.scopus.com/inward/record.url?scp=0032906990&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(98)00559-4

DO - 10.1016/S0306-4522(98)00559-4

M3 - Article

C2 - 10338300

AN - SCOPUS:0032906990

VL - 90

SP - 1325

EP - 1338

JO - Neuroscience

JF - Neuroscience

SN - 1873-7544

IS - 4

ER -