Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1)

Biochem J. 1998 Mar 15;330 ( Pt 3)(Pt 3):1417-22. doi: 10.1042/bj3301417.

Abstract

We report the identification of a unique repetitive sequence in the rat endothelial receptor for oxidized low-density lipoprotein (LOX-1) and unexpected blood-pressure-associated regulation of its expression, a new link between lipid metabolism and blood-pressure control. A rat aorta cDNA library was constructed and screened with a probe synthesized by degenerate PCR. Rat LOX-1 cDNA encoded a protein of 364 amino acids that showed approximately 60% similarity to its bovine and human counterparts. The protein consisted of intracellular N-terminal, transmembrane and extracellular lectin-like domains. Rat LOX-1 was unique in having three repeats of a 46-amino-acid motif between the transmembrane and lectin-like regions. Two isoforms of mRNA were found to be generated by alternative use of two polyadenylation signals in a tissue-specific manner. The 3'-untranslated region contained multiple A+U-rich elements for rapid degradation of mRNA. Northern-blot analysis revealed that LOX-1 mRNA was expressed predominantly in the lung. Quite unexpectedly, the expression was dramatically up-regulated in the aorta in hypertensive SHR-SP/Izm rats compared with very low levels in control WKY/Izm rats, suggesting a potential role for LOX-1 in the pathogenesis of hypertension as well as atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Aorta
  • Arteriosclerosis / physiopathology
  • Base Sequence
  • Blood Pressure*
  • Cattle
  • Endothelium, Vascular / metabolism*
  • Humans
  • Hypertension / genetics
  • Hypertension / physiopathology*
  • Lipoproteins, LDL / metabolism
  • Lung / metabolism
  • Male
  • Molecular Sequence Data
  • Organ Specificity
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, LDL / biosynthesis*
  • Receptors, LDL / chemistry
  • Receptors, LDL / genetics
  • Receptors, Oxidized LDL
  • Repetitive Sequences, Nucleic Acid*
  • Restriction Mapping
  • Scavenger Receptors, Class E
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transcription, Genetic*
  • Up-Regulation*
  • Vena Cava, Inferior

Substances

  • Lipoproteins, LDL
  • OLR1 protein, human
  • OLR1 protein, rat
  • Receptors, LDL
  • Receptors, Oxidized LDL
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein

Associated data

  • GENBANK/AB005900