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Am J Physiol Lung Cell Mol Physiol 274: L343-L350, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 3, L343-L350, March 1998

O2 regulates surfactant protein A mRNA transcription and stability in human fetal lung in vitro

Michael J. Acarregui1, Ashish R. Kumar2, Scott T. Penisten1, and Jeanne M. Snyder2

Departments of 1 Pediatrics and 2 Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City, Iowa 52242

The effect of O2 on surfactant protein (SP) A mRNA transcription and half-life was determined in midtrimester human fetal lung tissue cultured in either 20 (control) or 70% O2. Incubation of tissues in 70% O2 resulted in a 133% increase in SP-A mRNA transcription rate compared with control tissues. The SP-A mRNA half-life was increased by 54% in lung tissues cultured in 70% O2 vs. control tissues. Western blot analysis indicated a threefold increase in SP-A in the 70% O2 condition, demonstrating that O2 regulation of SP-A mRNA levels results in corresponding changes in SP-A levels. Primer extension assays were performed to determine whether the observed increase in SP-A mRNA levels is secondary to the preferential expression of one of the human SP-A genes, SP-A1 or SP-A2. Transcripts of both the SP-A1 and SP-A2 genes were increased ~100% in tissues maintained in 70% O2 compared with control tissues. These data demonstrate that O2 regulates human SP-A mRNA levels by both transcriptional and posttranscriptional mechanisms. Furthermore, because there is no differential effect of O2 on the expression of SP-A1 vs. SP-A2 mRNA, the properties of these genes that mediate regulation by O2 must be conserved between the two genes.

oxygen; messenger ribonucleic acid


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