Dr. Crawford et al., Oxidative stress causes a general, calcium-dependent degradation of mitochondrial polynucleotides, FREE RAD B, 25(9), 1998, pp. 1106-1111
Oxidative stress has many effects on biological cells, including the modula
tion of gene expression. Reactive oxygen species are known to up-regulate a
nd down-regulate RNA expression in prokaryotic and eukaryotic cells. We hav
e previously reported that a preferential and calcium-dependent down-regula
tion of mitochondrial RNAs occurs when HA-I hamster fibroblasts are exposed
to hydrogen peroxide. Here we extend these studies to determine whether th
is down-regulation is specific to mitochondria RNA or involves general poly
nucleotide degradation. Degradation and associated decreases in the levels
of 16S mitochondrial rRNA following exposure of cells to 400 mu M hydrogen
peroxide were found to be dependent on calcium at 2 and 5 h. Degradation of
mitochondrial genomic DNA was also observed following peroxide exposure, a
nd occurred at similar time points as for mitochondrial RNA degradation. As
with mitochondrial RNA degradation, this mitochondrial genomic DNA degrada
tion was dependent on calcium. These results indicate that-there is a gener
al, calcium-dependent degradation of mitochondrial polynucleotides followin
g exposure of HA-1 fibroblasts to oxidative stress, and suggest that a dram
atic shut-down in mitochondrial biosynthesis is an early-stage response to
oxidative stress. (C) 1998 Elsevier Science Inc.