Polynucleotide degradation during early stage response to oxidative stressis specific to mitochondria

Oxidative stress is known to modulate RNA expression in both prokaryotic an d eukaryotic cells. We have previously determined that a preferential and c alcium-dependent downregulation of mitochondrial RNA occurs in HA-1 hamster fibroblasts in response to hydrogen peroxide, and that this is accompanied by the degradation of mitochondrial genomic DNA. Here we extended these st udies to determine whether downregulation is specific to transcripts derive d from mitochondrial-encoded genes; to determine whether genomic DNA degrad ation occurs in the nucleus; and to compare overall polynucleotide stress r esponse with cellular growth arrest and apoptosis. We observed that nuclear genome-encoded mRNAs whose protein products are targeted for the electron transport chain of mitochondria were not degraded. Furthermore, early stage degradation of genomic DNA, assessed within the first 5 h of peroxide expo sure, was specific to mitochondria, as nuclear genomic DNA was not degraded under the same treatment conditions. These differential degradations occur red under conditions where extensive growth-arrest and moderate apoptosis w ere observed, and were accompanied by significant induction of the growth a rrest mRNAs gadd45, gadd153, and adapt15/gadd7. Combined, these results ind icate that there is a general degradation of mitochondrial- but not nuclear -polynucleotides during early stage response of HA-1 fibroblasts to oxidati ve stress. (C) 2000 Elsevier Science Inc.