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Modulation of mitochondrial gene expression in pulmonary epithelial cells exposed to oxidants.

Authors
Janssen-YM; Driscoll-KE; Timblin-CR; Hassenbein-D; Mossman-BT
Source
Environ Health Perspect 1998 Oct; 106(Suppl 5):1191-1195
NIOSHTIC No.
20030559
Abstract
Oxidants are important in the regulation of signal transduction and gene expression. Multiple classes of genes are transcriptionally activated by oxidants and are implicated in different phenotypic responses. In the present study, we performed differential mRNA display to elucidate genes that are induced or repressed after exposure of rat lung epithelial (RLE) cells to H2O2 or crocidolite asbestos, a pathogenic mineral that generates oxidants. After 8 or 24 hr of exposure, RNA was extracted, reverse transcribed, and amplified by polymerase chain reaction with degenerate primers to visualize alterations in gene expression. The seven clones obtained were sequenced and encoded the mitochondrial genes, NADH dehydrogenase subunits ND5 and ND6, and 16S ribosomal RNA. Evaluation of their expression by Northern blot analysis revealed increased expression of 16S rRNA after 1 or 2 hr of exposure to H2O2. At later time periods (4 and 24 hr), mRNA levels of 16S rRNA and NADH dehydrogenase were decreased in H2O2-treated RLE cells when compared to sham controls. Crocidolite asbestos caused increases in 16S rRNA levels after 8 hr of exposure, whereas after 24 hr of exposure to asbestos, 16S rRNA levels were decreased in comparison to sham controls. In addition to these oxidants, the nitric oxide generator spermine NONOate caused similar decreases in NADH dehydrogenase mRNA levels after 4 hr of exposure. The present data and previous studies demonstrated that all oxidants examined resulted in apoptosis in RLE cells during the time frame where alterations of mitochondrial gene expression were observed. As the mitochondrion is a major organelle that controls apoptosis, alterations in expression of mitochondrial genes may be involved in the regulation of apoptosis.
Keywords
Oxidation; Oxides; Laboratory-animals; Animals; Animal-studies; Lung-cells; Pulmonary-system; Asbestosis; Exposure-levels; Exposure-assessment; Ribonucleic-acids
CODEN
EVHPAZ
CAS No.
7722-84-1; 12001-28-4
Publication Date
19981001
Document Type
Journal Article
Email Address
yjanssen@zoo.uvm.edu
Funding Amount
75969
Funding Type
Grant
Fiscal Year
1999
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R03-OH-003467
ISSN
0091-6765
Source Name
Environmental Health Perspectives
State
VT
Performing Organization
Pathology University of Vermont Medical, Burlington, Vermont
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