Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the technique of differential plaque filter hybridization, a rat cDNA was isolated whose corresponding gene expression in the kidney was positively modulated up to threefold by sodium depletion. This mRNA was more abundantly expressed in the kidneys of 17-week-old spontaneously hypertensive rats than those of age-matched Wistar-Kyoto rats. The putative protein encoded by this cDNA is a homologue of cyclophilin, a cytosolic binding protein for cyclosporin A. This cyclophilin-like protein mRNA was expressed in all the tissues examined, including the adrenal, atrium, brain, kidney, liver, lung, spleen, and ventricle. Sodium depletion in rats increased the expression level of this mRNA not only in the kidney but also in the liver. The administration of cyclosporin A in rats increased the expression level of this mRNA in the kidneys and livers. By virtue of its possible involvement in sodium homeostasis and its homology to cyclophilin, this molecule might have significant implications in the mechanism of cyclosporine-induced renal insufficiency and hypertension.
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PMID:Molecular cloning of a complementary DNA to rat cyclophilin-like protein mRNA. 219 66

Rat cyclophilin-like protein (Cy-LP) is a candidate hypertension gene initially identified by differential hybridization and implicated in renal mechanisms of salt retention and high blood pressure. We report the molecular characterization of rat cyclophilin B (CypB) and demonstrate, through sequence analysis and an allele-specific polymerase chain reaction primer assay, that CypB but not Cy-LP is expressed in rat kidney. CypB is an endoplasmic reticulum-localized prolyl-isomerase that interacts with elongation initiation factor 2-beta, an important regulator of protein translation and a central component of the endoplasmic reticulum stress response to hypoxia or ATP depletion. Active renal transport of sodium is increased in the spontaneously hypertensive rat (SHR), and there is evidence that this coincides with hypoxia and ATP depletion in the renal cortex. In the present studies we have examined expression of CypB in rat proximal tubules, which contributes to the increased renal sodium reabsorption in this model of hypertension. We report that CypB transcript abundance is significantly elevated in proximal convoluted tubules from SHR compared with the control Wistar-Kyoto strain. This upregulation occurs in weanling animals and precedes the development of hypertension, indicating that it is not a simple response to hypertension in SHR. Further, CypB expression is also higher in a proximal tubule cell line derived from SHR compared with a similar line derived from Wistar-Kyoto rats, indicating that this difference is genetically determined. No sequence differences were observed in the CypB cDNA from these 2 strains. These observations suggest that a genetically determined alteration in proximal tubules from SHR occurs that leads to increased expression of CypB. In view of evidence linking CypB to the regulation of elongation initiation factor-2, the upregulation of CypB may result from metabolic stress.
Hypertension 2000 Apr
PMID:Cyclophilin B expression in renal proximal tubules of hypertensive rats. 1077 69