Vascular expression of extracellular superoxide dismutase in atherosclerosis

Tohru Fukai, Zorina S. Galis, Xiao Ping Meng, Sampath Parthasarathy, David G. Harrison

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

We characterized a novel form of extracellular superoxide dismutase (ecSOD) in atherosclerotic vessels. Specific activity and protein expression of ecSOD was increased two- to threefold in apo E-deficient compared with control aortas. RNase protection assays demonstrated that the expected ecSOD transcript was not increased in either apo E-deficient mice or cholesterol- fed LDL receptor-deficient mice, but that a second, lower molecular weight transcript was present and became predominant as atherosclerosis progressed. Sequence analysis revealed that this novel ecSOD has a 10-bp deletion in the 3' untranslated region and an asparagine to aspartic acid mutation at amino acid 21. Studies of isolated macrophages and immunohistochemistry suggested that the truncated ecSOD transcript was expressed by lipid-laden but not control macrophages. Recombinant wild-type and novel ecSODs expressed in Sf9 cells exhibited similar SOD activities. These experiments show that ecSOD expression is increased in atherosclerotic vessels and that this is characterized by an alteration in mRNA and protein structure. Further, the source of this altered ecSOD is likely the lipid-laden macrophage. The enzymatic properties of this novel ecSOD may have important implications for the function of the lipid-laden macrophage and the atherosclerotic process.

Original languageEnglish (US)
Pages (from-to)2101-2111
Number of pages11
JournalJournal of Clinical Investigation
Volume101
Issue number10
DOIs
StatePublished - May 15 1998

Fingerprint

Superoxide Dismutase
Blood Vessels
Atherosclerosis
Macrophages
Apolipoproteins E
Lipids
Sf9 Cells
LDL Receptors
Asparagine
3' Untranslated Regions
Ribonucleases
Aspartic Acid
Sequence Analysis
Aorta
Proteins
Molecular Weight
Immunohistochemistry
Cholesterol
Amino Acids
Messenger RNA

Keywords

  • Foam cell macrophage
  • Low density lipoprotein receptor
  • RNase protection assay
  • Superoxide dismutase
  • apo E

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Vascular expression of extracellular superoxide dismutase in atherosclerosis. / Fukai, Tohru; Galis, Zorina S.; Meng, Xiao Ping; Parthasarathy, Sampath; Harrison, David G.

In: Journal of Clinical Investigation, Vol. 101, No. 10, 15.05.1998, p. 2101-2111.

Research output: Contribution to journalArticle

Fukai, T, Galis, ZS, Meng, XP, Parthasarathy, S & Harrison, DG 1998, 'Vascular expression of extracellular superoxide dismutase in atherosclerosis', Journal of Clinical Investigation, vol. 101, no. 10, pp. 2101-2111. https://doi.org/10.1172/JCI2105
Fukai, Tohru ; Galis, Zorina S. ; Meng, Xiao Ping ; Parthasarathy, Sampath ; Harrison, David G. / Vascular expression of extracellular superoxide dismutase in atherosclerosis. In: Journal of Clinical Investigation. 1998 ; Vol. 101, No. 10. pp. 2101-2111.
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