Regulation of superoxide dismutase genes: Implications in disease

Lu Miao, Daret K. St. Clair

Research output: Contribution to journalReview articlepeer-review

656 Scopus citations

Abstract

Numerous short-lived and highly reactive oxygen species (ROS) such as superoxide (O2{radical dot}-), hydroxyl radical, and hydrogen peroxide are continuously generated in vivo. Depending upon concentration, location, and intracellular conditions, ROS can cause toxicity or act as signaling molecules. The cellular levels of ROS are controlled by antioxidant enzymes and small-molecule antioxidants. As major antioxidant enzymes, superoxide dismutases (SODs), including copper-zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase, and extracellular superoxide dismutase, play a crucial role in scavenging O2{radical dot}-. This review focuses on the regulation of the sod genes coding for these enzymes, with an emphasis on the human genes. Current knowledge about sod structure and regulation is summarized and depicted as diagrams. Studies to date on genes coding for Cu/ZnSOD (sod1) are mostly focused on alterations in the coding region and their associations with amyotrophic lateral sclerosis. Evaluation of nucleotide sequences reveals that regulatory elements of the sod2 gene reside in both the noncoding and the coding region. Changes associated with sod2 lead to alterations in expression levels as well as protein function. We also discuss the structural basis for the changes in SOD expression associated with pathological conditions and where more work is needed to establish the relationship between SODs and diseases.

Original languageEnglish
Pages (from-to)344-356
Number of pages13
JournalFree Radical Biology and Medicine
Volume47
Issue number4
DOIs
StatePublished - Aug 15 2009

Bibliographical note

Funding Information:
Work for this review was supported by NIH Grants CA 49797 and CA 73599.

Keywords

  • Free radicals
  • Gene regulation
  • Oxidative stress-related disease
  • Superoxide dismutase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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