Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1).
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.
Nagase
M
M
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo 112, Japan.
Hirose
S
S
Fujita
T
T
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta; D001161:Arteriosclerosis / Q000503:physiopathology; D001483:Base Sequence; D001794:Blood Pressure; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D051131:Receptors, Oxidized LDL; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D051127:Scavenger Receptors, Class E; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D015854:Up-Regulation; D014682:Vena Cava, Inferior
D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; C495136:OLR1 protein, rat; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein