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排序方式: 共有109条查询结果,搜索用时 31 毫秒
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Lieneke F.M. Ariëns Jorien van der Schaft Lotte S. Spekhorst Daphne S. Bakker Geertruida L.E. Romeijn Tessa A. Kouwenhoven Marijke Kamsteeg Angelique N. Voorberg Albert J. Oosting Ilona de Ridder Annemieke Sloeserwij Inge Haeck Judith L. Thijs Marie L.A. Schuttelaar Marjolein S. de Bruin-Weller 《Journal of the American Academy of Dermatology》2021,84(4):1000-1009
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An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. 总被引:10,自引:1,他引:9
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S M Mulders D G Bichet J P Rijss E J Kamsteeg M F Arthus M Lonergan M Fujiwara K Morgan R Leijendekker P van der Sluijs C H van Os P M Deen 《The Journal of clinical investigation》1998,102(1):57-66
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. 相似文献
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Birgitta C. P. Hüsken Margreet B. Vroom Erik-Jan F. Timmenga Martin Pfaffendorf Pieter A. Van Zwieten 《European journal of pharmacology》1995,287(3):313-316
The effect of levcromakalim, an ATP-sensitive K+ channel opener, on isolated subcutaneous arteries from mammary tissues obtained from female patients undergoing reconstructive breast surgery was investigated. The small arteries were preserved in the University of Wisconsin (UW) solution. The contractile responses to K+ and 9,11-dideoxy-11,9-epoxy-methano-prostaglandin F2 (U46619) and the relaxant responses to levcromakalim and to the endothelium-dependent vasodilator, methacholine, in these arteries remained fully intact after preservation in UW solution for at least 5 days. The pD2 value and maximal relaxation obtained from the concentration-response curve of levcromakalim (n = 7) were 5.78 ± 0.23 and 81 ± 6%, respectively. The vasodilator effect of levcromakalim was significantly antagonised by the ATP-sensitive K+ channel blocker, glibenclamide (1 and 3 μM). In conclusion, isolated human arteries contain ATP-sensitive K+ channels, which can be modulated by K+ channel openers and blockers. Subcutaneous small arteries, as used in our experiments, appear to be very suitable for pharmacological experiments. 相似文献
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de Mattia F Savelkoul PJ Bichet DG Kamsteeg EJ Konings IB Marr N Arthus MF Lonergan M van Os CH van der Sluijs P Robertson G Deen PM 《Human molecular genetics》2004,13(24):3045-3056
Vasopressin regulates water homeostasis through insertion of homotetrameric aquaporin-2 (AQP2) water channels in the apical plasma membrane of renal cells. AQP2 mutations cause recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. Until now, all AQP2 mutants in recessive NDI were shown to be misfolded, retained in the endoplasmic reticulum (ER) and unable to interact with wild-type (wt)-AQP2, whereas AQP2 mutants in dominant NDI are properly folded and interact with wt-AQP2, but, due to the mutation, cause missorting of the wt-AQP2/mutant complex. Here, patients of two families with recessive NDI appeared compound heterozygotes for AQP2-A190T or AQP2-R187C mutants, together with AQP2-P262L. As mutations in the AQP2 C-tail, where P262 resides, usually cause dominant NDI, the underlying cell-biological mechanism was investigated. Upon expression in oocytes, AQP2-P262L was a properly folded and functional aquaporin in contrast to the classical mutants, AQP2-R187C and AQP2-A190T. Expressed in polarized cells, AQP2-P262L was retained in intracellular vesicles and did not localize to the ER. Upon co-expression, however, AQP2-P262L interacted with wt-AQP2, but not with AQP2-R187C, resulting in a rescued apical membrane expression of AQP2-P262L. In conclusion, our study reveals a novel cellular phenotype in recessive NDI in that AQP2-P262L acts as a mutant in dominant NDI, except for that its missorting is overruled by apical sorting of wt-AQP2. Also, it demonstrates for the first time that the recessive inheritance of a disease involving a channel can be due to two cell-biological mechanisms. 相似文献