المؤلفون: van Os CH; Department of Cell Physiology, University of Nijmegen, The Netherlands., Deen PM

المصدر: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 1998 Jul; Vol. 13 (7), pp. 1645-51.

نوع المنشور: Journal Article; Review

بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print Cited Medium: Print ISSN: 0931-0509 (Print) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE

مواضيع طبية MeSH: Membrane Glycoproteins*, Body Water/*metabolism , Ion Channels/*physiology , Kidney/*physiology, Amino Acid Sequence ; Animals ; Aquaporin 1 ; Aquaporin 2 ; Aquaporin 6 ; Aquaporins/chemistry ; Aquaporins/genetics ; Aquaporins/physiology ; Blood Group Antigens ; Diabetes Insipidus, Nephrogenic/genetics ; Diabetes Insipidus, Nephrogenic/physiopathology ; Eye Proteins/physiology ; Humans ; Ion Channels/chemistry ; Ion Channels/genetics ; Kidney Concentrating Ability/genetics ; Kidney Concentrating Ability/physiology ; Models, Molecular ; Molecular Sequence Data

المؤلفون: Mulders SM; Department Of Cell Physiology, University of Nijmegen, 6500 HB Nijmegen, The Netherlands., Bichet DG, Rijss JP, Kamsteeg EJ, Arthus MF, Lonergan M, Fujiwara M, Morgan K, Leijendekker R, van der Sluijs P, van Os CH, Deen PM

المصدر: The Journal of clinical investigation [J Clin Invest] 1998 Jul 01; Vol. 102 (1), pp. 57-66.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Print ISSN: 0021-9738 (Print) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins*, Diabetes Insipidus, Nephrogenic/*genetics , Golgi Apparatus/*metabolism , Ion Channels/*physiology, Adult ; Aquaporin 2 ; Aquaporin 6 ; Biological Transport ; Female ; Humans ; Ion Channels/genetics ; Mutation ; Phosphorylation

مستخلص: Mutations in the aquaporin-2 (AQP2) water channel gene cause autosomal recessive nephrogenic diabetes insipidus (NDI). Here we report the first patient with an autosomal dominant form of NDI, which is caused by a G866A transition in the AQP2 gene of one allele, resulting in a E258K substitution in the C-tail of AQP2. To define the molecular cause of NDI in this patient, AQP2-E258K was studied in Xenopus oocytes. In contrast to wild-type AQP2, AQP2-E258K conferred a small increase in water permeability, caused by a reduced expression at the plasma membrane. Coexpression of wild-type AQP2 with AQP2-E258K, but not with an AQP2 mutant in recessive NDI (AQP2-R187C), revealed a dominant-negative effect on the water permeability conferred by wild-type AQP2. The physiologically important phosphorylation of S256 by protein kinase A was not affected by the E258K mutation. Immunoblot and microscopic analyses revealed that AQP2-E258K was, in contrast to AQP2 mutants in recessive NDI, not retarded in the endoplasmic reticulum, but retained in the Golgi compartment. Since AQPs are thought to tetramerize, the retention of AQP2-E258K together with wild-type AQP2 in mixed tetramers in the Golgi compartment is a likely explanation for the dominant inheritance of NDI in this patient.

المؤلفون: Deen PM; Department of Cell Physiology, University of Nijmegen, The Netherlands., Rijss JP, Mulders SM, Errington RJ, van Baal J, van Os CH

المصدر: Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 1997 Oct; Vol. 8 (10), pp. 1493-501.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Wolters Kluwer Health, on behalf of the American Society of Nephrology Country of Publication: United States NLM ID: 9013836 Publication Model: Print Cited Medium: Print ISSN: 1046-6673 (Print) Linking ISSN: 10466673 NLM ISO Abbreviation: J Am Soc Nephrol Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins*, Deamino Arginine Vasopressin/*metabolism , Ion Channels/*genetics , Ion Channels/*metabolism , Kidney Tubules, Collecting/*metabolism, Animals ; Aquaporin 2 ; Aquaporin 6 ; Biological Transport, Active ; Cell Line ; Cyclic AMP/metabolism ; Dogs ; Immunohistochemistry ; Kidney Tubules, Collecting/cytology ; Kinetics ; Models, Biological ; Osmosis ; Permeability ; RNA, Messenger/genetics ; Transfection ; Water/metabolism

مستخلص: Water transport across the mammalian collecting tubule is regulated by vasopressin-dependent aquaporin-2 insertion into and retrieval from the apical cell membrane. To establish a cell line that properly expresses aquaporin-2 and its hormone-dependent shuttling, Madin-Darby canine kidney cells were stably transfected with an aquaporin-2 expression construct. Cells of a representative clone (wild-type 10 [WT-10]) were grown on semipermeable supports, and transcellular osmotic water permeability (Pf; in microm/s +/- SEM) was measured. The basal Pf of WT-10 cells, which was lowered with indomethacin, increased from 10.6 +/- 0.8 to 35.7 +/- 1.2 upon incubation with 1-desamino-8-D-arginine vasopressin (dDAVP). This increase coincided with the translocation of aquaporin-2 from an intracellular compartment to the apical membrane. The Pf of untransfected cells (6.5 +/- 0.8) was unchanged by dDAVP. Kinetic studies with WT-10 cells revealed that maximal Pf was obtained within 30 min after dDAVP addition, which remained elevated for at least 90 min. Intracellular cAMP levels peaked within 5 min after dDAVP admission and decreased to basal levels within 45 min. After preincubation with dDAVP, the Pf decreased within 15 min after dDAVP washout and returned to basal levels within 75 min. In conclusion, the WT-10 cells mimic the vasopressin-regulated transcellular water transport and aquaporin-2 translocation as found in collecting duct cells to a great extent, and therefore constitute an in vitro cell model that can be used to study the regulation of transcellular water transport in detail and provide a simplified test system for screening putative aquaporin-2 blockers.

المؤلفون: Mulders SM; Department of Cell Physiology, University of Nijmegen, The Netherlands., Rijss JP, Hartog A, Bindels RJ, van Os CH, Deen PM

المصدر: The American journal of physiology [Am J Physiol] 1997 Sep; Vol. 273 (3 Pt 2), pp. F451-6.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: American Physiological Society Country of Publication: United States NLM ID: 0370511 Publication Model: Print Cited Medium: Print ISSN: 0002-9513 (Print) Linking ISSN: 00029513 NLM ISO Abbreviation: Am J Physiol Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins* , Cysteine*, Ion Channels/*physiology , Mercuric Chloride/*pharmacology , Oocytes/*physiology, Amino Acid Sequence ; Animals ; Aquaporin 1 ; Aquaporin 2 ; Aquaporin 6 ; Blood Group Antigens ; Cell Membrane Permeability ; Conserved Sequence ; Diabetes Insipidus/genetics ; Diabetes Insipidus/physiopathology ; Female ; Humans ; Ion Channels/chemistry ; Ion Channels/drug effects ; Models, Structural ; Oocytes/drug effects ; Point Mutation ; Protein Structure, Secondary ; Rats ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/drug effects ; Transcription, Genetic ; Xenopus laevis

مستخلص: To discriminate between water transport of of aquaporin-2 (AQP2) mutants in nephrogenic diabetes insipidus and that of an AQP2 molecule used to drag them to the oolemma, we investigated the mercury sensitivity of wild-type and AQP2 C181S proteins in oocytes. Incubation with HgCl2 inhibited the osmotic water permeability (Pf) of human (h) AQP2 by 40%, whereas inhibition of hAQP1 was 75%. Oocytes expressing hAQP1 C189S revealed a Pf comparable to wild-type hAQP1, but mercury sensitivity was lost. In contrast, no increase in Pf was obtained when hAQP2 C181S was expressed. Also, expression of rat AQP2 C181A and C181S mutants did not increase the Pf, which contrasts with published observations. Immunocytochemistry and immunoblotting revealed that only AQP1, AQP1 C189S, and AQP2 were targeted to the plasma membrane and that AQP2 mutant proteins are retarded in the endoplasmic reticulum. In conclusion, water transport through AQP2 is less sensitive to mercury inhibition than through AQP1. Furthermore, substitution of the mercury-sensitive cysteine for a serine results in an impaired routing of human and rat AQP2. Similar mutations have no effect on AQP1 function, which is indicative of structural differences between AQP1 and AQP2.

المؤلفون: Deen PM; Department of Cell Physiology, University of Nijmegen, The Netherlands., Nielsen S, Bindels RJ, van Os CH

المصدر: Pflugers Archiv : European journal of physiology [Pflugers Arch] 1997 Apr; Vol. 433 (6), pp. 780-7.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Springer Country of Publication: Germany NLM ID: 0154720 Publication Model: Print Cited Medium: Print ISSN: 0031-6768 (Print) Linking ISSN: 00316768 NLM ISO Abbreviation: Pflugers Arch Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins*, Cell Membrane Permeability/*physiology , Ion Channels/*biosynthesis, 1-Methyl-3-isobutylxanthine/pharmacology ; Animals ; Aquaporin 1 ; Blotting, Northern ; Blotting, Southern ; Cell Membrane Permeability/drug effects ; Cell Membrane Permeability/genetics ; Dogs ; Immunoblotting ; Ion Channels/genetics ; Kidney/cytology ; Kidney/drug effects ; Kidney/metabolism ; LLC-PK1 Cells ; Microscopy, Immunoelectron ; Osmolar Concentration ; Phosphodiesterase Inhibitors/pharmacology ; RNA, Messenger/biosynthesis ; Swine ; Tetradecanoylphorbol Acetate/pharmacology ; Transfection

مستخلص: Aquaporin-1 is present in the apical and basolateral membranes in proximal tubules and descending limbs of Henlé's loop. In order ot be able to study the routing of Aquaporin-1 and the regulation of Aquaporin-1-mediated transcellular water flow, we stably transfected LLC-PK1 and MDCK-HRS cell lines with an Aquaporin-1 expression construct. LLC-PK1 clone 7 and MDCK clone K integrated two and one copies, respectively, which was reflected in the amount of Aquaporin-1 mRNA expressed in both clones. The Aquaporin-1 protein levels, however, were similar. In both clones, immuno-electronmicroscopy showed extensive labelling of Aquaporin-1 on the basolateral plasma membrane, endosomal vesicles and the apical plasma membrane, including the microvilli. To measure transcellular water permeation, a simple method was applied using phenol-red as a cell-impermeant marker of concentration. In contrast to the native cell lines, both clones revealed a high transcellular osmotic water permeability, which could not be influenced by forskolin add/3-isobutyl-1-methylxanthine (IBMX) or the phorbol ester 12-O-tetradecanoyl 13-acetate (TPA). After glutaraldehyde fixation, it was inhibitable by HgCl2. These results indicate that targeting of Aquaporin-1 to the apical and basolateral plasma membrane is independent of cell type and show for the first time that water flow through a cultured epithelium can be blocked by mercurial compounds.

المؤلفون: Deen PM, Mulders SM, Kansen SM, van Os CH

المصدر: Science (New York, N.Y.) [Science] 1997 Mar 07; Vol. 275 (5305), pp. 1491; author reply 1492.

نوع المنشور: Comment; Letter

بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Print ISSN: 0036-8075 (Print) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins* , Cell Membrane Permeability*/drug effects, Cations/*metabolism , Ion Channels/*physiology , Water/*metabolism, 1-Methyl-3-isobutylxanthine/pharmacology ; Animals ; Aquaporin 1 ; Blood Group Antigens ; Colforsin/pharmacology ; Cyclic AMP/metabolism ; Humans ; Ion Channels/genetics ; Ion Transport ; Oocytes ; Patch-Clamp Techniques ; RNA, Complementary/genetics ; Xenopus

المؤلفون: Mulders SM; Department of Cell Physiology, University of Nijmegen, The Netherlands., Knoers NV, Van Lieburg AF, Monnens LA, Leumann E, Wühl E, Schober E, Rijss JP, Van Os CH, Deen PM

المصدر: Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 1997 Feb; Vol. 8 (2), pp. 242-8.

نوع المنشور: Case Reports; Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Wolters Kluwer Health, on behalf of the American Society of Nephrology Country of Publication: United States NLM ID: 9013836 Publication Model: Print Cited Medium: Print ISSN: 1046-6673 (Print) Linking ISSN: 10466673 NLM ISO Abbreviation: J Am Soc Nephrol Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins* , Point Mutation*, Diabetes Insipidus, Nephrogenic/*genetics , Diabetes Insipidus, Nephrogenic/*metabolism , Ion Channels/*genetics , Ion Channels/*metabolism, Adolescent ; Adult ; Animals ; Aquaporin 2 ; Aquaporin 6 ; Child, Preschool ; Female ; Genes, Recessive ; Humans ; In Vitro Techniques ; Male ; Oocytes/metabolism ; Xenopus

مستخلص: Nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine in response to vasopressin. The autosomal recessive form of NDI is caused by mutations in the AQP2 gene, encoding the vasopressin-regulated water channel of the kidney collecting duct. This report presents three new mutations in the AQP2 gene that cause NDI, resulting in A147T-, T126M-, or N68S-substituted AQP2 proteins. Expression of the A147T and T126M mutant AQP2 proteins in Xenopus oocytes revealed a relatively small, but significant increase in water permeability, whereas the water permeability of N68S expressing oocytes was not increased. cRNA encoding missense and wild-type AQP2 were equally stable in oocytes. Immunoblots of oocyte lysates showed that only the A147T mutant protein was less stable than wild-type AQP2. The mutant AQP2 proteins showed, in addition to the wild-type 29-kd band, an endoplasmic reticulum-retarded form of AQP2 of approximately 32 kd. Immunoblotting and immunocytochemistry demonstrated only intense labeling of the plasma membranes of oocytes expressing wild-type AQP2. In summary, two mutant AQP2 proteins encoded in NDI are functional water channels. Therefore, the major cause underlying autosomal recessive NDI is the misrouting of AQP2 mutant proteins.

المؤلفون: Mulders SM; Department of Cell Physiology, University of Nijmegen, The Netherlands., van Lieburg AF, Monnens LA, Knoers NV, Deen PM, van Os CH

المصدر: European journal of clinical investigation [Eur J Clin Invest] 1996 Dec; Vol. 26 (12), pp. 1041-50.

نوع المنشور: Journal Article; Review

بيانات الدورية: Publisher: Wiley Country of Publication: England NLM ID: 0245331 Publication Model: Print Cited Medium: Print ISSN: 0014-2972 (Print) Linking ISSN: 00142972 NLM ISO Abbreviation: Eur J Clin Invest Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins* , Membrane Proteins*, Ion Channels/*genetics , Ion Channels/*physiology, Amino Acid Sequence ; Animals ; Aquaporin 1 ; Aquaporin 2 ; Aquaporin 3 ; Aquaporin 4 ; Aquaporin 5 ; Aquaporin 6 ; Blood Group Antigens ; Chromosome Mapping ; Humans ; Ion Channels/chemistry ; Models, Molecular ; Molecular Sequence Data ; Sequence Alignment ; Sequence Deletion ; Structure-Activity Relationship

المؤلفون: Knoers NV; Department of Human Genetics, University Hospital, Nijmegen, The Netherlands., van Os CH

المصدر: Current opinion in nephrology and hypertension [Curr Opin Nephrol Hypertens] 1996 Jul; Vol. 5 (4), pp. 353-8.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Review

بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9303753 Publication Model: Print Cited Medium: Print ISSN: 1062-4821 (Print) Linking ISSN: 10624821 NLM ISO Abbreviation: Curr Opin Nephrol Hypertens Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins* , Mutation*, Diabetes Insipidus, Nephrogenic/*genetics , Diabetes Insipidus, Nephrogenic/*physiopathology , Ion Channels/*genetics , Receptors, Vasopressin/*genetics, Amino Acid Sequence ; Animals ; Aquaporin 2 ; Aquaporin 6 ; Female ; Genes, Recessive ; Genetic Carrier Screening ; Genetic Counseling ; Humans ; Ion Channels/chemistry ; Ion Channels/physiology ; Male ; Molecular Sequence Data ; Protein Structure, Secondary ; Receptors, Vasopressin/chemistry ; Receptors, Vasopressin/physiology ; X Chromosome

مستخلص: Nephrogenic diabetes insipidus is a rare genetic disorder characterized by insensitivity of the distal nephron to the antidiuretic effect of arginine vasopressin. Two different molecular defects underlying this disease have so far been identified. Mutations in the gene encoding the vasopressin type-2 receptor cause the X-chromosomal form of the disease, whereas mutations in the gene encoding the vasopressin-dependent water channel aquaporin-2 are responsible for the autosomal recessive, and (in some cases) an autosomal dominant type of the disease. Functional analysis of naturally occurring mutations in the vasopressin type-2 receptor and aquaporin-2 have increased the insight into the structure and function of both proteins and have led to substantial progress in understanding the cellular mechanisms underlying the concentrating ability of the kidney. Some female carriers of a vasopressin type-2 receptor mutation may show complete manifestation of nephrogenic diabetes insipidus, probably as a result of skewed X-inactivation. The recent findings in nephrogenic diabetes insipidus research have considerable impact for diagnosis of and genetic counselling for this disease.

المؤلفون: Deen PM; Department of Cell Physiology, University of Nijimegen, The Netherlands., van Aubel RA, van Lieburg AF, van Os CH

المصدر: Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 1996 Jun; Vol. 7 (6), pp. 836-41.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Wolters Kluwer Health, on behalf of the American Society of Nephrology Country of Publication: United States NLM ID: 9013836 Publication Model: Print Cited Medium: Print ISSN: 1046-6673 (Print) Linking ISSN: 10466673 NLM ISO Abbreviation: J Am Soc Nephrol Subsets: MEDLINE

مواضيع طبية MeSH: Aquaporins*, Diabetes Insipidus, Nephrogenic/*urine , Ion Channels/*urine, Adult ; Aquaporin 1 ; Aquaporin 2 ; Aquaporin 6 ; Blood Group Antigens ; Child ; Child, Preschool ; Diabetes Insipidus, Nephrogenic/genetics ; Diuresis ; Female ; Humans ; Immunoblotting ; Ion Channels/genetics ; Male ; Middle Aged ; Mutation ; Receptors, Vasopressin/genetics ; Reference Values

مستخلص: Hereditary nephrogenic diabetes insipidus (NDI) is caused by mutations in either the X-chromosomal gene encoding the vasopressin V2-receptor or in the autosomal gene encoding aquaporin-2. Expressed in Xenopus oocytes, the AQP2 gene mutations found in NDl have been shown to reduce the stability of the encoded protein. This study investigated the in vivo stability of mutant and wild-type aquaporin-2 proteins by measuring their excretion in urine of NDl patients and healthy individuals. On immunoblots, the urine samples from healthy volunteers revealed clear aquaporin-1 and aquaporin-2 signals in antidiuretic but not diuretic states. In the urine of a female patient, whose NDl is explained by low expression of the wild-type V2-receptor gene, aquaporin-2 excretion was high and comparable with that in a healthy individual during antidiuresis. In the urine of a male patient with a non-sense mutation in the V2-receptor gene, a weak aquaporin-2 signal was detected. In NDl patients with mutations in the aquaporin-2 gene, aquaporin-2 could not be detected in urine, suggesting a low stability of mutant aquaporin-2 proteins. In four out of seven NDl patients, aquaporin-1 excretion was relatively high, which suggests a compensatory increase in proximal reabsorption in NDl.