| Normalization of proliferation and tight junction formation in bladder epithelial cells from patients with interstitial cystitis/painful bladder syndrome by d-proline and d-pipecolic acid derivatives of antiproliferative factor. | |
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MedLine Citation:
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PMID: 21352500 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Interstitial cystitis/painful bladder syndrome is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that interstitial cystitis/painful bladder syndrome bladder epithelial cells make a glycopeptide antiproliferative factor or 'APF' (Neu5Acα2-3Galβ1-3GalNAcα-O-TVPAAVVVA) that induces abnormalities in normal cells similar to those in interstitial cystitis/painful bladder syndrome cells in vitro, including decreased proliferation, decreased tight junction formation, and increased paracellular permeability. We screened inactive APF derivatives for their ability to block antiproliferative activity of asialylated-APF ('as-APF') in normal bladder cells and determined the ability of as-APF-blocking derivatives to normalize tight junction protein expression, paracellular permeability, and/or proliferation of interstitial cystitis/painful bladder syndrome cells. Only two of these derivatives [Galβ1-3GalNAcα-O-TV-(d-pipecolic acid)-AAVVVA and Galβ1-3GalNAcα-O-TV-(d-proline)-AAVVVA] blocked as-APF antiproliferative activity in normal cells (p < 0.001 for both). Both of these antagonists also 1) significantly increased mRNA expression of ZO-1, occludin, and claudins 1, 4, 8, and 12 in interstitial cystitis/painful bladder syndrome cells by qRT-PCR; 2) normalized interstitial cystitis/painful bladder syndrome epithelial cell tight junction protein expression and tight junction formation by confocal immunofluorescence microscopy; and 3) decreased paracellular permeability of (14) C-mannitol and (3) H-inulin between confluent interstitial cystitis/painful bladder syndrome epithelial cells on Transwell plates, suggesting that these potent APF antagonists may be useful for the development as interstitial cystitis/painful bladder syndrome therapies. |
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Authors:
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Susan Keay; Piotr Kaczmarek; Chen-Ou Zhang; Kristopher Koch; Zoltan Szekely; Joseph J Barchi; Christopher Michejda |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2011-04-27 |
Journal Detail:
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Title: Chemical biology & drug design Volume: 77 ISSN: 1747-0285 ISO Abbreviation: Chem Biol Drug Des Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-16 Completed Date: 2011-09-16 Revised Date: 2011-12-16 |
Medline Journal Info:
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Nlm Unique ID: 101262549 Medline TA: Chem Biol Drug Des Country: England |
Other Details:
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Languages: eng Pagination: 421-30 Citation Subset: IM |
Copyright Information:
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Published 2011. This article is a US Government work and is in the public domain in the USA. |
Affiliation:
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Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. skeay@medicine.umaryland.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Carbohydrate Sequence Cell Membrane Permeability / drug effects Cell Proliferation / drug effects Cells, Cultured Cystitis, Interstitial / drug therapy*, metabolism, pathology Epithelial Cells / drug effects*, metabolism, pathology Gene Expression Regulation / drug effects Glycoproteins / antagonists & inhibitors, chemistry*, metabolism, pharmacology* Humans Pipecolic Acids / chemistry Proline / chemistry Tight Junctions / drug effects*, metabolism, pathology Urinary Bladder / cytology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK52596/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Glycoproteins; 0/Pipecolic Acids; 0/antiproliferative factor APF, human; 147-85-3/Proline; 535-75-1/pipecolic acid |
| Comments/Corrections | |
Comment In:
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J Urol. 2011 Dec;186(6):2264-5
[PMID:
22078590
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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