Recently,a paper by Kim et al.[1] in Nature Medicine magazine in January,2013 showed that apelin (also known as ApLN) inhibits fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) expression to ameliorate pulm...
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Recently,a paper by Kim et al.[1] in Nature Medicine magazine in January,2013 showed that apelin (also known as ApLN) inhibits fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) expression to ameliorate pulmonary hypertension by regulating the expression of miR-424 and *** study revealed the molecular mechanism of apelin in inhibiting the process of pulmonary arterial hypertension (pAH) and discovered the role of apelin in regulating miRNA generation for the first *** functions in the transcriptional regulation of gene expression to control cellular processes,miRNA is a key regulatory factor of protein expression,but the generation and regulation mechanism of miRNA is still *** novel findings bring us inspiration for further research,especially on the mechanism of miRNA *** on revealing endogenous active substance,which regulates the generation of miRNAs or revealing miRNAs that regulate the expression of apelin,may bring more breakthroughs in the future.
The transport of the angiotensin II receptor antagonist rosarian and its interaction with organic anion transport were examined in the isolated perfused rabbit proximal tubule. Losartan reversibly inhibited the secret...
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The transport of the angiotensin II receptor antagonist rosarian and its interaction with organic anion transport were examined in the isolated perfused rabbit proximal tubule. Losartan reversibly inhibited the secretion of para-aminohippurate (pAH) in a concentration-dependent manner (IC50 = 15 +/- 0.5 mu M). Other angiotensin II receptor antagonists also inhibited pAH secretion with similar potencies: eprosartan, 11 +/- 2.3 mu M;irbesartan, 17 +/- 2.2 mu M, and valsartan 3 +/- 0.6 mu M. [H-3]Losartan was secreted by the proximal tubule by a saturable and probenecid-sensitive mechanism. The affinity of losartan for the organic anion transporter (K-m = 12.3 +/- 1.8 mu M) was significantly greater than that of pAH (K-m = 88.5 +/- 10.7 mu M) [H-3]losartan secretion was stimulated in the presence of cu-ketoglutarate, suggesting that losartan, like pAH, enters the cell in exchange for a dicarboxylate. These results demonstrate that losartan and probably other nonpeptide angiotensin II receptor antagonists are secreted by an organic anion transporter that is similar to, if not identical with, the classic pAH transporter.
In the present study, we investigated the transport of ochratoxin A (OTA) by kidney-specific organic anion transporter 1 (OAT1). When expressed in Xenopus laevis oocytes, OAT1 mediated sodium-independent uptake of OTA...
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In the present study, we investigated the transport of ochratoxin A (OTA) by kidney-specific organic anion transporter 1 (OAT1). When expressed in Xenopus laevis oocytes, OAT1 mediated sodium-independent uptake of OTA (K-m = 2.1 mu M). piroxicam, which has been shown to prevent the nephrotoxicity of OTA, inhibited OAT1-mediated uptake of OTA. By contrast, another protective compound, aspartame, did not. Using a cell line derived from the mouse kidney terminal proximal tubule (S3) transfected with OAT1 cDNA, we investigated the transport of OTA and also its effect on cell proliferation and cell viability. S3 cells expressing OAT1 mediated the saturable transport of OTA (K-m = 0.57 mu M). Cell proliferation was suppressed in S3 cells expressing OAT1 when exposed to 2 and 10 mu M OTA. This suppression was rescued by the coaddition of 1 mM p-aminohippurate in the media. The present study indicates that OTA is transported by OAT1 and that the accumulation of OTA via OAT1 in proximal tubular cells is the primary event in the development of OTA nephrotoxicity.
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