Functional assessment of sodium chloride cotransporter NCC mutants in polarized mammalian epithelial cells
In conclusion, this system allows the activity, cellular localization, and abundance of wild-type or mutant NCC to be examined in the same polarized mammalian expression system in a rapid, easy, and low-cost fashion. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Rosenbaek, L. L., Rizzo, F., MacAulay, N., Staub, O., Fenton, R. A. Tags: INNOVATIVE METHODOLOGY Source Type: research
Urine RAS components in mice and people with type 1 diabetes and chronic kidney disease
In conclusion, in mice with streptozotocin-induced diabetes and in humans with DKD, urine concentrations and enzymatic activities of several RAS components are concordantly increased, consistent with enhanced RAS activity and greater angiotensin II formation. ACEI use was associated with a specific reduction in urine ACE activity, not ACE protein concentration, suggesting that it may be a marker of exposure to this widely-used therapy. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Wysocki, J., Goodling, A., Burgaya, M., Whitlock, K., Ruzinski, J., Batlle, D., Afkarian, M. Tags: RESEARCH ARTICLE Source Type: research
The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome after kidney transplantation
Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine, and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest in this pathway because of its proinflammatory nature, and drugs interfering in it have received increasing attention. We aimed to investigate whether serum and urinary parameters of the tryptophan/kynurenine pathway, and particularly cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long-term outcome in renal transplant recipients (RTR). Data were collected in outpatient RTR with a functioning graft for >1 yr. Tryptophan, kynurenine, ...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: de Vries, L. V., Minovic, I., Franssen, C. F. M., van Faassen, M., Sanders, J.-S. F., Berger, S. P., Navis, G., Kema, I. P., Bakker, S. J. L. Tags: RESEARCH ARTICLE Source Type: research
Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na+-glucose cotransporter
We report in the present study a detailed functional characterization of human SGLT2 in coexpression with human MAP17 in Xenopus laevis oocytes. Addition of external glucose generates a large inward current in the presence of Na, confirming an electrogenic transport mechanism. At a membrane potential of –50 mV, SGLT2 affinity constants for glucose and Na are 3.4 ± 0.4 and 18 ± 6 mM, respectively. The change in the reversal potential of the cotransport current as a function of external glucose concentration clearly confirms a 1:1 Na-to-glucose transport stoichiometry. SGLT2 is selective for glucose and &...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Coady, M. J., Wallendorff, B., Lapointe, J.-Y. Tags: RESEARCH ARTICLE Source Type: research
Protein disulfide isomerase regulates renal AT1 receptor function and blood pressure in rats
The role and mechanism of renal protein disulfide isomerase (PDI) in blood pressure regulation has not been tested before. Here, we test this possibility in Sprague-Dawley rats. Rats were treated with PDI inhibitor bacitracin (100 mg·kg–1 ip·day–1 for 14 days), and then blood pressure and renal angiotensin II type 1 (AT1) receptor function were determined in anesthetized rats. Renal AT1 receptor function was determined as the ability of candesartan (an AT1 receptor blocker) to increase diuresis and natriuresis. A second set of vehicle- and bacitracin-treated rats was used to determine biochemical ...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Wang, X., Asghar, M. Tags: RESEARCH ARTICLE Source Type: research
The effects of angiotensin-(1-7) on the exchanger NHE3 and on [Ca2+]i in the proximal tubules of spontaneously hypertensive rats
The acute effects of angiotensin-1–7 [ANG-(1–7)] on the reabsorptive bicarbonate flow (JHCO3–) were evaluated using stationary microperfusion in vivo in the proximal tubules of spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using a microelectrode sensitive to H+. In WKY rats, the control JHCO3– was 2.40 ± 0.10 nmol·cm–2·s–1 (n = 120); losartan (10–7 M) or A779 (10–6 M, a specific Mas antagonist), alone or in combination with losartan, decreased the JHCO3–. ANG-(1–7) had biphasic effects on JHCO3...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Castelo-Branco, R. C., Leite-Dellova, D. C. A., Fernandes, F. B., Malnic, G., de Mello-Aires, M. Tags: RESEARCH ARTICLE Source Type: research
Luminal ANG II is internalized as a complex with AT1R/AT2R heterodimers to target endoplasmic reticulum in LLC-PK1 cells
ANG II has many biological effects in renal physiology, particularly in Ca2+ handling in the regulation of fluid and solute reabsorption. It involves the systemic endocrine renin-angiotensin system (RAS), but tissue and intracrine ANG II are also known. We have shown that ANG II induces heterodimerization of its AT1 and AT2 receptors (AT1R and AT2R) to stimulate sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity. Thus, we investigated whether ANG II-AT1R/AT2R complex is formed and internalized, and also examined the intracellular localization of this complex to determine how its effect might be exerted on renal intr...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Ferrao, F. M., Cardoso, L. H. D., Drummond, H. A., Li, X. C., Zhuo, J. L., Gomes, D. S., Lara, L. S., Vieyra, A., Lowe, J. Tags: RESEARCH ARTICLE Source Type: research
Podocyte-specific knockout of cyclooxygenase 2 exacerbates diabetic kidney disease
Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of Type 1 diabetes mellitus (Akita mice). Podocyte-specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in nondiabetic mice. Albuminuria was significantly increased in wild-type (WT) and KO Akita mice compared with nondiabetic con...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Wang, L., Sha, Y., Bai, J., Eisner, W., Sparks, M. A., Buckley, A. F., Spurney, R. F. Tags: RESEARCH ARTICLE Source Type: research
ATP-citrate lyase is essential for high glucose-induced histone hyperacetylation and fibrogenic gene upregulation in mesangial cells
The goal of this study was to address the role of ATP-citrate lyase (ACL), an enzyme that converts citrate to acetyl-CoA, in high glucose (HG)-induced histone acetylation and profibrotic gene expression. Our recent ChIP-Seq studies have demonstrated that HG induces genome-wide histone hyperacetylation in mesangial cells (MCs). Here, we showed that exposure of MCs to HG markedly increased histone acetylation at the H3K9/14 and H3K18 marks and induced the expression of potent profibrotic factors TGF-β1, TGF-β3, and connective tissue growth factor (CTGF). The induction of these profibrotic factors was further enhanc...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Deb, D. K., Chen, Y., Sun, J., Wang, Y., Li, Y. C. Tags: RESEARCH ARTICLE Source Type: research
Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-{kappa}B-TNF-{alpha} and TGF-{beta}1-MAPK-fibronectin pathways
Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5–20 mg/k...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Malik, S., Suchal, K., Khan, S. I., Bhatia, J., Kishore, K., Dinda, A. K., Arya, D. S. Tags: RESEARCH ARTICLE Source Type: research
Protein phosphatase 2C is responsible for VP-induced dephosphorylation of AQP2 serine 261
In conclusion, PP2C activity is required for S261 AQP2 dephosphorylation upon VP stimulation, which occurs independently of S256 phosphorylation. Understanding the pathways involved in modulating PP2C will help elucidate the role of S261 in cellular events involving AQP2. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Cheung, P. W., Ueberdiek, L., Day, J., Bouley, R., Brown, D. Tags: RESEARCH ARTICLE Source Type: research
Inhibition of cholinergic neurotransmission by {beta}3-adrenoceptors depends on adenosine release and A1-receptor activation in human and rat urinary bladders
The direct detrusor relaxant effect of β3-adrenoceptor agonists as a primary mechanism to improve overactive bladder symptoms has been questioned. Among other targets, activation of β3-adrenoceptors downmodulate nerve-evoked acetylcholine (ACh) release, but there is insufficient evidence for the presence of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a retrograde messenger via prejunctional A1 receptors to explain inhibition of cholinergic activity by β3-adrenoceptors. Isoprenaline (1 µM) de...
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Silva, I., Costa, A. F., Moreira, S., Ferreirinha, F., Magalhaes-Cardoso, M. T., Calejo, I., Silva-Ramos, M., Correia-de-Sa, P. Tags: RESEARCH ARTICLE Source Type: research
Effect of sodium nitrite on renal function and sodium and water excretion and brachial and central blood pressure in healthy subjects: a dose-response study
In conclusion, intravenous NaNO2 induced a dose-dependent reduction of brachial and central BP. The hemodynamic effect was not mediated by the renin-angiotensin-aldosterone system. NaNO2 infusion resulted in a vasopressin-independent decrease in CH2O and urine output but no change in urinary sodium excretion or GFR. The lack of increase in cGMP accompanying the increase in NO2– suggests a direct effect of nitrite or nitrate on the renal tubules and vascular bed with little or no systemic conversion to NO. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - August 2, 2017 Category: Urology & Nephrology Authors: Rosenbaek, J. B., Al Therwani, S., Jensen, J. M., Mose, F. H., Wandall-Frostholm, C., Pedersen, E. B., Bech, J. N. Tags: RESEARCH ARTICLE Source Type: research
Developmental changes in contractile responses to cholinergic stimuli: role of calcium sensitization and related pathways
This study was performed to analyze the developmental changes in bladder response to cholinergic stimulation in detail, highlighting calcium sensitization (CS) and its related pathways. Rats were divided into three groups in accordance with reported time of developmental milestones (newborns, days 1–4; youngsters, days 5–14; and grown-ups, days 15–28). Following cholinergic stimulation (carbachol, 5 µM), the contractile response to detrusor was analyzed with respect to three phases (initial phasic, tonic, and superimposed phasic contractions). Contractile responses were analyzed by their dynamic and...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Im, Y. J., Lee, J. K., Lee, S. H., Oh, S.-J., Park, K. Tags: RESEARCH ARTICLE Source Type: research
Ovariectomy uncovers purinergic receptor activation of endothelin-dependent natriuresis
We recently reported that natriuresis produced by renal medullary salt loading is dependent on endothelin (ET)-1 and purinergic (P2) receptors in male rats. Because sex differences in ET-1 and P2 signaling have been reported, we decided to test whether ovarian sex hormones regulate renal medullary ET-1 and P2-dependent natriuresis. The effect of medullary NaCl loading on Na+ excretion was determined in intact and ovariectomized (OVX) female Sprague-Dawley rats with and without ET-1 or P2 receptor antagonism. Isosmotic saline (284 mosmol/kgH2O) was infused in the renal medullary interstitium of anesthetized rats during a ba...
Source: AJP: Renal Physiology - August 1, 2017 Category: Urology & Nephrology Authors: Gohar, E. Y., Kasztan, M., Becker, B. K., Speed, J. S., Pollock, D. M. Tags: RESEARCH ARTICLE Source Type: research
