Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate the effects of the anti-inflammatory hormone alpha-melanocyte-stimulating hormone (alpha-MSH) treatment on renal function and expression of aquaporins (AQPs) and Na-K-ATPase in the kidney in response to 24 h of bilateral ureteral obstruction (BUO) or release of BUO (BUO-R). In rats with 24-h BUO, immunoblotting revealed that downregulation of AQP2 and AQP3 was attenuated (AQP2: 38 +/- 5 vs. 13 +/- 4%; AQP3: 44 +/- 3 vs. 19 +/- 4% of sham levels; P < 0.05), whereas downregulation of Na-K-ATPase was prevented by alpha-MSH treatment (Na-K-ATPase: 94 +/- 7 vs. 35 +/- 5% of sham levels; P < 0.05). Immunocytochemistry confirmed the changes in AQP1 and Na-K-ATPase expression. Renal tubular cell apoptosis was confirmed in BUO kidneys, and alpha-MSH treatment virtually completely abolished apoptosis. Furthermore, we measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Forty-eight hours after BUO-R demonstrated that alpha-MSH treatment almost completely prevented the decrease in GFR (nontreated: 271 +/- 50; alpha-MSH: 706 +/- 85; sham: 841 +/- 105 microl x min(-1).100 g body wt(-1), P < 0.05) and ERPF (nontreated: 1,139 +/- 217; alpha-MSH: 2,598 +/- 129; sham: 2,633 +/- 457 microl x min(-1).100 g body wt(-1), P < 0.05). alpha-MSH treatment also partly prevented the downregulation of AQP1 and Na-K-ATPase expression in rats after BUO-R for 48 h. In conclusion, alpha-MSH treatment significantly prevents impairment in renal function and also prevents downregulation of AQP2, AQP3, and Na-K-ATPase during BUO or AQP1 and Na-K-ATPase after BUO-R, demonstrating a marked renoprotective effect of alpha-MSH treatment in conditions with urinary tract obstruction.
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PMID:alpha-MSH prevents impairment in renal function and dysregulation of AQPs and Na-K-ATPase in rats with bilateral ureteral obstruction. 1618 88

The molecular mechanisms of radiation-induced xerostomia remain unclear. The purpose of this study was to investigate the alterations of aquaporins (AQPs) and Na(+)/K(+)-ATPase in irradiated rat submandibular glands and to test the hypothesis that down-regulation of AQP5 expression in irradiated salivary glands is one of the mechanisms of radiation-induced xerostomia. Saliva from control and irradiated rat submandibular glands was analyzed. The mRNA level of AQP5 in the submandibular glands was assessed by semi-quantitative RT-PCR and in situ hybridization. The protein expression of AQP5, AQP1 and Na(+)/K(+)-ATPase was determined by Western blotting and immunohistochemistry. The body weight, submandibular gland weight, and saliva secretion of irradiated rats significantly decreased by 12, 24 and 32% on day 3 and 24, 16 and 38% on day 30 postirradiation, respectively. There was a significant increase in the protein concentration and osmolality of saliva in irradiated rats on days 3 and 30 postirradiation. However, there was no significant difference between irradiated and control rats in total saliva protein secretion. RT-PCR analysis showed that mRNA expression of AQP5 was significantly down-regulated by 37 and 51% in irradiated rats on days 3 and 30 postirradiation, respectively. Immunoblotting showed that the AQP5 protein level was decreased by 40 and 60% in irradiated glands, in contrast to the slight reductions of AQP1 and Na(+)/K(+)-ATPase proteins. Immunohistochemical analysis demonstrated that loss of AQP5 protein occurred throughout the irradiated glands, while no significant reduction was detected in AQP1 and Na(+)/ K(+)-ATPase labeling density. These results suggest that the preferential down-regulation of AQP5 with minor effects on AQP1 and Na(+)/K(+)-ATPase may contribute to radiation-induced salivary dysfunction.
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PMID:Decreased saliva secretion and down-regulation of AQP5 in submandibular gland in irradiated rats. 1680 68

The cerebrospinal fluid (CSF) provides mechanical and chemical protection of the brain and spinal cord. This review focusses on the contribution of the choroid plexus epithelium to the water and salt homeostasis of the CSF, i.e. the secretory processes involved in CSF formation. The choroid plexus epithelium is situated in the ventricular system and is believed to be the major site of CSF production. Numerous studies have identified transport processes involved in this secretion, and recently, the underlying molecular background for some of the mechanisms have emerged. The nascent CSF consists mainly of NaCl and NaHCO(3), and the production rate is strictly coupled to the rate of Na(+) secretion. In contrast to other secreting epithelia, Na(+) is actively pumped across the luminal surface by the Na(+),K(+)-ATPase with possible contributions by other Na(+) transporters, e.g. the luminal Na(+),K(+),2Cl(-) cotransporter. The Cl(-) and HCO(3) (-) ions are likely transported by a luminal cAMP activated inward rectified anion conductance, although the responsible proteins have not been identified. Whereas Cl(-) most likely enters the cells through anion exchange, the functional as well as the molecular basis for the basolateral Na(+) entry are not yet well-defined. Water molecules follow across the epithelium mainly through the water channel, AQP1, driven by the created ionic gradient. In this article, the implications of the recent findings for the current model of CSF secretion are discussed. Finally, the clinical implications and the prospects of future advances in understanding CSF production are briefly outlined.
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PMID:Water and solute secretion by the choroid plexus. 1712 21

We report the immunolocalization of aquaporins (AQPs) 1, 4, and 6 in the human auditory and vestibular endorgans. A rapid protocol was applied to audiovestibular endorgans microdissected from postmortem human temporal bones from six subjects (ages ranging from 75 to 97 years) with no history of audiovestibular disease. Temporal bones were fixed in formalin, and the endorgans were immediately microdissected. Cryostat sections were obtained from audiovestibular endorgans and were subjected to double-immunohistochemical staining with antibodies against AQPs and several cellular markers. In the human cochlea, AQP1 immunoreactivity was localized to the fibrocytes of the spiral ligament and the sub-basilar tympanic cells; AQP4 immunoreactivity was localized to the outer sulcus cells, Hensen's cells, and Claudius' cells; AQP6 immunoreactivity was localized to the apical portion of interdental cells in the spiral limbus. In the vestibular endorgans (macula utriculi and cristae), AQP1 was localized to fibrocytes and blood vessels of the underlying stroma and trabecular perilymphatic tissue; AQP4 immunoreactivity was localized to the basal pole of vestibular supporting cells; AQP6 was localized to the apical portion of vestibular supporting cells. Cochlear and vestibular hair cells and nerve fibers were not immunoreactive for any AQP. Supporting cells were identified with antibodies against glial fibrilar acidic protein. Nerve fibers and terminals were identified with antibodies against neurofilaments and Na(+)K(+)ATPase. The high degree of conservation of AQP expression in the human inner ear suggests that AQPs play a critical role in inner ear water homeostasis.
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PMID:Immunohistochemical localization of aquaporins in the human inner ear. 1731 86

We investigated whether alpha-lipoic acid (alpha-LA), an antioxidant, attenuates the ischemia-reperfusion (I/R)-induced dysregulation of these transporters. Both renal pedicles of male Sprague-Dawley rats were clamped for 40 min. alpha-LA (80 mg/kg) was administered intraperitoneally before and immediately after induction of ischemia. After 2 days, the expression of aquaporins (AQPs), sodium transporters, and nitric oxide synthases (NOS) was determined in the kidney by immunoblotting and immunohistochemistry. The expression of endothelin-1 (ET-1) mRNA was determined by real-time PCR. Activities of adenylyl cyclase and guanylyl cyclase were measured by stimulated generation of cAMP and cGMP, respectively. The expression of AQP1-3 as well as that of the alpha(1)-subunit of Na-K-ATPase, type 3 Na/H exchanger, Na-K-2Cl cotransporter, and Na-Cl cotransporter was markedly decreased in response to I/R. The expression of type VI adenylyl cyclase was decreased in I/R-injured rats, which was counteracted by the treatment of alpha-LA. AVP-stimulated cAMP generation was blunted in I/R rats and was then ameliorated by alpha-LA treatment. alpha-LA treatment attenuated the downregulation of AQPs and sodium transporters. The expression of endothelial NOS was decreased in I/R rats, which was prevented by alpha-LA. The cGMP generation in response to sodium nitroprusside was blunted in I/R rats, which was also significantly prevented by alpha-LA. The mRNA expression of ET-1 was increased, which was recovered to the control level by alpha-LA treatment. In conclusion, alpha-LA treatment prevents I/R-induced dysregulation of AQPs and sodium transporters in the kidney, possibly through preserving normal activities of local AVP/cAMP, nitric oxide/cGMP, and ET systems.
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PMID:Effects of alpha-lipoic acid on ischemia-reperfusion-induced renal dysfunction in rats. 1803 50

Aquaporin-2 (AQP2), the vasopressin-regulated water channel in collecting duct principal cells, plays a key role in the regulation of body water balance. We aimed to isolate high-affinity peptide ligands that bind to immunoisolated AQP2-expressing plasma membrane (PM) or intracellular vesicle (ICV) preparations from rat kidney by the in vitro phage display technique. Immunoblotting revealed that AQP2 was exclusively expressed in the immunoisolated AQP2 membrane fractions (PM and ICV), compared with the nonimmunoisolated or preimmune IgG pulldown rat kidney samples. Moreover, AQP1 or H+-ATPase (B1 subunit) expression was minimal in the immunoisolated AQP2 membrane fractions, indicating the specificity of AQP2 membrane isolation. A phage peptide library based on T7 415-1b phage vector displaying CX7C was constructed. After three rounds of biopanning, seven phage clones of high frequency were selected, which showed high affinity to the AQP2-containing PM or ICV fractions compared with a nonrecombinant T7 insertless phage clone. In contrast, these phage clones showed lower affinity to H+-ATPase-containing fractions. Fluorescein-conjugated peptide labeling was associated with intracellular compartment and PM of primary cultured inner medullary collecting duct cells, relative to absent or very weak labeling with fluorescein-conjugated control peptide. Library analyses demonstrated proteins that had motifs homologous to the peptide ligands, albeit with a high probability of a random match due to short peptide sequences. In summary, we applied the in vitro phage display technique to identify high-affinity peptide ligands to AQP2-expressing membranes. Library analyses identified proteins having homologous motifs, which need to be examined for involvement in AQP2 trafficking and regulation.
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PMID:A novel method of ligand peptidomics to identify peptide ligands binding to AQP2-expressing plasma membranes and intracellular vesicles of rat kidney. 1848 Jan 84

Although deoxycorticosterone acetate (DOCA)-salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA-salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of alpha-1 subunit of Na,K-ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA-salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.
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PMID:Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA-salt hypertensive rats. 1942 59

Following chorda tympani denervation (CTD, parasympathetomy), the protein levels of aquaporin5 (AQP5) as well as AQP1 and Na(+)K(+)ATPase alpha-subunit in the rat submandibular gland (SMG) were found to be decreased significantly. However, the level of another membrane protein, dipeptidyl peptidase IV was not affected by CTD, suggesting a selective reduction of AQP5, AQP1, and Na(+)K(+)ATPase alpha -subunit proteins by CTD. However, the AQP5 mRNA level was scarcely affected by CTD, which suggested that transcription process of AQP5 was unaffected by this operation. AQP5 protein was shown to be degraded in vitro by the extract of the SMG obtained from normal rat; inhibitor experiments in vitro suggested cathepsin B was a responsible enzyme. Co-localization of AQP5 and LAMP-2, a lysosomal marker, implicated AQP5 is degraded in lysosomes. A significant increase in the protein levels of LC3-II, an autophagy marker, at day 1 after CTD, and co-localization of the LC3 protein and AQP5, suggested that CTD activated autophagy of SMG, leading to AQP5 degradation.
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PMID:Down-regulation of submandibular gland AQP5 following parasympathetic denervation in rats. 2022

Meniere's disease is nearly invariably associated with endolymphatic hydrops (the net accumulation of water in the inner ear endolymphatic space). Vestibular maculae utriculi were acquired from patients undergoing surgery for Meniere's disease and acoustic neuroma and from autopsy (subjects with normal hearing and balance). Quantitative immunostaining was conducted with antibodies against aquaporins (AQPs) 1, 4, and 6, Na(+)K(+)ATPase, Na(+)K(+)2Cl co-transporter (NKCC1), and alpha-syntrophin. mRNA was extracted from the surgically acquired utricles from subjects with Meniere's disease and acoustic neuroma to conduct quantitative real-time reverse transcription with polymerase chain reaction for AQP1, AQP4, and AQP6. AQP1 immunoreactivity (-IR) was located in blood vessels and fibrocytes in the underlying stroma, without any apparent alteration in Meniere's specimens when compared with acoustic neuroma and autopsy specimens. AQP4-IR localized to the epithelial basolateral supporting cells in Meniere's disease, acoustic neuroma, and autopsy. In specimens from subjects with Meniere's disease, AQP4-IR was significantly decreased compared with autopsy and acoustic neuroma specimens. AQP6-IR occurred in the sub-apical vestibular supporting cells in acoustic neuroma and autopsy samples. However, in Meniere's disease specimens, AQP6-IR was significantly increased and diffusely redistributed throughout the supporting cell cytoplasm. Na(+)K(+)ATPase, NKCC1, and alpha-syntrophin were expressed within sensory epithelia and were unaltered in Meniere's disease specimens. Expression of AQP1, AQP4, or AQP6 mRNA did not differ in vestibular endorgans from patients with Meniere's disease. Changes in AQP4 (decreased) and AQP6 (increased) expression in Meniere's disease specimens suggest that the supporting cell might be a cellular target.
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PMID:Immunohistochemical localization and mRNA expression of aquaporins in the macula utriculi of patients with Meniere's disease and acoustic neuroma. 2046 9

The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 +/- 0.1 in dDAVP+losartan (LSDL) vs. 1.1 +/- 0.1 ml.100 g(-1).day(-1) in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 +/- 0.5 in LSDL vs. 6.8 +/- 0.5 ml/min in LSD, P > 0.05). The urine output, however, was significantly increased in LSDL (2.5 +/- 0.2 vs. 1.8 +/- 0.2 ml.100 g(-1).day(-1), P < 0.05) in association with decreased urine osmolality (2,600 +/- 83 vs. 3,256 +/- 110 mosmol/kgH(2)O, P < 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 +/- 6 vs. 176 +/- 10% in LSD, P < 0.01), p-AQP2 (177 +/- 13 vs. 214 +/- 12% in LSD, P < 0.05), and AQP3 (134 +/- 14 vs. 177 +/- 11% in LSD, P < 0.05) in LSDL compared with LSD. The expressions of AQP1, the alpha(1)- and gamma-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.
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PMID:Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration. 2057 79


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