Gender difference in kidney electrolyte transport. I. Role of AT receptor in thiazide-sensitive Na-Cl cotransporter activity and expression in male and female mice.

We studied gender differences in Na-Cl cotransporter (NCC) activity and expression in wild-type (WT) and AT receptor knockout (KO) mice. In renal clearance experiments, urine volume (UV), glomerular filtration rate, absolute Na (E) and K (E), and fractional Na (FE) and K excretion were measured and compared at peak changes after bolus intravenous injection of hydrochlorothiazide (HCTZ; 30 mg/kg). In WT, females responded more strongly than males to HCTZ, with larger fractional increases of UV (7.

Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.

Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake.

Impaired self-renewal and increased colitis and dysplastic lesions in colonic mucosa of AKR1B8-deficient mice.

Purpose: Ulcerative colitis and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Aldo-keto reductase 1B10 (AKR1B10) is specifically expressed in the colonic epithelium, but downregulated in colorectal cancer. This study was aimed to investigate the etiopathogenic role of AKR1B10 in ulcerative colitis and CAC.

Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation.

Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs.

Regulation of glomerulotubular balance: II: impact of angiotensin II on flow-dependent transport.

Underlying glomerulotubular balance (GTB) is the impact of axial flow to regulate Na(+) and HCO(3)(-) transport by modulating Na(+)-H(+) exchanger 3 (NHE3) and H-ATPase activity. It is not known whether the cascade of events following a change in flow relies on local angiotensin (ANG II) generation or receptor availability. Mouse tubules were microperfused in vitro at flows of 5 and 20 nl/min, and net fluid (J(v)) and HCO(3)(-) (J(HCO3)) absorption and cell height were measured.

Regulation of glomerulotubular balance. I. Impact of dopamine on flow-dependent transport.

In response to volume expansion, locally generated dopamine decreases proximal tubule reabsorption by reducing both Na/H-exchanger 3 (NHE3) and Na-K-ATPase activity. We have previously demonstrated that mouse proximal tubules in vitro respond to changes in luminal flow with proportional changes in Na(+) and HCO(3)(-) reabsorption and have suggested that this observation underlies glomerulotubular balance. In the present work, we investigate the impact of dopamine on the sensitivity of reabsorptive fluxes to changes in luminal flow.

Differential expression of uridine phosphorylase in tumors contributes to an improved fluoropyrimidine therapeutic activity.

Abrogation of uridine phosphorylase (UPase) leads to abnormalities in pyrimidine metabolism and host protection against 5-fluorouracil (5-FU) toxicity. We elucidated the effects on the metabolism and antitumor efficacy of 5-FU and capecitabine (N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) in our UPase knockout (UPase(-/-)) model. Treatment with 5-FU (85 mg/kg) or capecitabine (1,000 mg/kg) five days a week for four weeks caused severe toxicity and structural damage to the intestines of wild-type (WT) mice, but not in UPase(-/-) animals.

Acid regulation of NaDC-1 requires a functional endothelin B receptor.

Metabolically generated acid is the major physiological stimulus for increasing proximal tubule citrate reabsorption, which leads to a decrease in citrate excretion. The activity of the Na-citrate cotransporter, NaDC-1, is increased in vivo by acid ingestion and in vitro by an acidic pH medium. In opossum kidney cells the acid stimulatory effect and the ability of endothelin-1 (ET-1) to stimulate NaDC-1 activity are both blocked by the endothelin B (ET(B)) receptor antagonist, BQ788.

Activation of Stat1, IRF-1, and NF-kappaB is required for the induction of uridine phosphorylase by tumor necrosis factor-alpha and interferon-gamma.

Uridine phosphorylase (UPase) has been shown to be induced in various human and murine tumors and could potentially serve as a specific target for the modulation of tumor-selectivity of fluoropyrimidines. However, the signaling mechanisms underlying the regulation of UPase gene expression have not been determined. In this study, we investigated the effects of IFN-gamma on the regulation of TNF-alpha-induced UPase activity and have uncovered the molecular mechanisms of this potentiation, utilizing murine EMT6 breast cancer cells.

Uridine phosphorylase in breast cancer: a new prognostic factor?

Uridine phosphorylase (UPase) is an enzyme that converts the pyrimidine nucleoside uridine into uracil. Upon availability of ribose-1-phosphate, UPase can also catalyze the formation of nucleosides from uracil as well as from 5-fluorouracil, therefore involved in fluoropyrimidine metabolism. UPase gene expression is strictly controlled at the promoter level by oncogenes, tumor suppressor genes, and cytokines.

Modulation of uridine phosphorylase gene expression by tumor necrosis factor-alpha enhances the antiproliferative activity of the capecitabine intermediate 5'-deoxy-5-fluorouridine in breast cancer cells.

Uridine phosphorylase (UPase) has been shown to play an important role in the antineoplastic activity of 5-fluorouracil (5-FU) and in the anabolism of its oral prodrug, capecitabine, through the conversion of 5'-deoxy-5-fluorouridine (5'-DFUR) into 5-FU. In this study, we investigated the effect of tumor necrosis factor-alpha (TNF-alpha) on UPase gene expression and 5'-DFUR antiproliferative activity and elucidated the involved signal transduction pathway. Our data indicate that TNF-alpha significantly induced UPase mRNA expression and its enzymatic activity in EMT6 murine breast cancer cells, leading to an enhanced cytotoxicity of 5'-DFUR.

[Establishment and identification of the gene cell line transfected aldose reductase like gene and its drug resistance to drugs containing carbonyl group].

Objective: To investigate the relationship between aldose reductase like protein (ARL-1) gene overexpressed in HCC cells and drug-resistance of the cell to drugs containing carbonyl group.

Methods: To establish ARL-1 stable expression positive cell line, eukaryotic expression vectors containing ARL-1 gene cDNA were transfected into Hep cell mediated by lipofect AMINE. The positive monoclones were determined by PCR and RT-PCR, respectively.