Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced sodium reabsorption by the kidney has a significant role in the development of genetic hypertension. In the spontaneously hypertensive rat (SHR) model of genetic hypertension, the enhanced sodium reabsorption likely arises from abnormal hormonal regulation of tubular transport. Since hormonal signaling pathways are coupled frequently via GTP binding proteins, one explanation for hormonal abnormalities in SHR would be a defect in a GTP binding protein or proteins. Recent work has suggested that the regulation of Na+,K(+)-ATPase activity by cholera toxin-sensitive GTP binding proteins is abnormal in SHR. The purpose of the present studies was to clone the alpha S-subunit, which is the subunit ADP ribosylated by cholera toxin, of GS protein to determine whether it is abnormal in SHR. Reverse transcription-polymerase chain reaction was able to detect mRNA for alpha S in both Wistar-Kyoto (WKY) rats and SHR. Northern analysis indicated that equivalent amounts of alpha S mRNA were present in WKY rats and SHR. S1 nuclease analysis demonstrated that there was no difference in the amount of alpha S short and long forms between WKY rats and SHR. Subcloning and sequencing of polymerase chain reaction products from WKY rats and SHR indicated that the alpha S forms present in renal cortex were identical. ADP ribosylation studies with cholera toxin demonstrated the presence of equivalent amounts of alpha S protein in WKY rats and SHR. Taken together, these results suggest that the abnormal regulation of Na+,K(+)-ATPase activity by a cholera toxin-sensitive pathway in SHR does not arise from a defect in the alpha S subunit.
Hypertension 1994 Nov
PMID:Cloning of the alpha-subunit of GS protein from spontaneously hypertensive rats. 796 19

Recent studies have documented the presence of a complete renin-angiotensin system in the proximal tubule of the kidney: however, little is known about the regulation of renin in this proximal tubular system. Therefore, we performed the present studies to learn whether the behavior of the renin system in cultured proximal tubule is similar to that of the juxtaglomerular renin system. Basal renin secretion from rabbit proximal tubular cells in primary culture was low and not affected by isoproterenol (10(-5) mol/L), diltiazem (10(-5) mol/L), or a zero-calcium bath (O nmol/L). Only the calcium ionophore A23187 (10(-4) mol/L) significantly reduced renin secretion in these cells (from 2.44 +/- 0.37 to 1.14 +/- O.08 ng angiotensin I/mg protein per hour, P<.05). When the proximal tubular cells were lysed so the effects of the test agents on intracellular renin content could be assessed, isoproterenol caused a significant twofold (107 percent) increase (from 2.02 +/- 0.56 to 4.18 +/- 0.81 ng angiotensin I/mg protein per hour, P<.05), whereas diltiazem, A23187, and zero- and high-calcium baths did not produce a significant change. The effects of these agents on renin mRNA were examined in rabbit and rat proximal tubular cells in primary culture with the use of an S1 nuclease protection assay. Densitometry analysis of renin mRNA and either GAPDH mRNA (rat) or alpha-actin (rabbit) showed no significant alterations in renin mRNA abundance. In summary, these results confirm the presence of renin mRNA in cultured proximal tubular cells and suggest that a low-level, constitutive secretion of renin occurs in this system that is decreased by A23187. Moreover, the results also suggest that proximal tubular renin is regulated, albeit differently from the juxtaglomerular renin system. Finally, short-term increments in proximal tubular renin occur without a change in renin mRNA.
Hypertension 1996 Jun
PMID:Renin regulation in cultured proximal tubular cells. 864 45

Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells show exaggerated growth and increased expression of platelet-derived growth factor (PDGF) A-chain mRNA. We examined the effect of methylene methylimino linkage of antisense oligodeoxynucleotide, a novel modification of antisense oligodeoxynucleotide designed to increase nuclease resistance, to PDGF A-chain on the exaggerated growth of vascular smooth muscle cells from SHR. Methylene methylimino-linked oligodeoxynucleotide provided complete resistance against S1 nuclease. Methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain resulted in a rapid inhibition of basal DNA synthesis of vascular smooth muscle cells from SHR. This inhibition was much greater than that produced by phosphorothioate linkage of antisense oligodeoxynucleotide to PDGF A-chain. The methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain may prove useful in the treatment of arterial proliferative diseases including hypertension.
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PMID:Effect of methylene methylimino linkage of antisense oligonucleotide to the platelet-derived growth factor A-chain on growth of vascular smooth muscle cells from spontaneously hypertensive rats. 1076 64