Extracellular superoxide dismutase (SOD3): tissue-specific expression, genomic characterization, and...

We have isolated and characterized over 10,000 bp of the human EC SOD gene (SOD3 or EC 1.15.1.1) and its 5'- and 3'-flanking regions. Human genomic Southern blot analysis supports the existence of a single gene, without evidence for pseudogenes. The human EC SOD gene spans approximately 5900 bp. The gene can be divided into 3 exons and 2 introns. The 720-bp coding region is uninterrupted and located within exon 3. The 560 bp 5' to the transcription start site were sequenced. No obvious TATA box was identified. A variety of conserved cis elements were identified by database searching. Exon 3 is surrounded by an Alu-J repetitive element in reverse orientation at the 5' and by an Alu-Sx repetitive element in the 3'-flanking DNA. The relative levels of EC SOD tissue-specific expression were determined by RNA gel blot analysis. Adult heart, placenta, pancreas, and lung had the most expression, followed by kidney, skeletal muscle, and liver. Little EC SOD message was found in the brain. A second unique mRNA, approximately 4.2 kb in length, was highly expressed in skeletal muscle. When tissue enzyme activity is compared to relative mRNA levels, there is a marked disparity in the brain, pancreas, and lung, suggesting that these tissues have enhanced affinity for circulating EC SOD or translate the EC SOD message more efficiently than other tissues. These results indicate that the EC SOD gene contains unique transcriptional regulatory elements and that its expression may be regulated at the post-transcriptional or post-translational level. The characterization of the human EC SOD gene should now allow the development of further insights into its biology and provide the basis for studies of its role in human heritable disorders.