LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 3 of total 3

Search options

  1. Article ; Online: Lithocholic bile acid induces apoptosis in human nephroblastoma cells: a non-selective treatment option.

    Trah, Julian / Arand, Jonas / Oh, Jun / Pagerols-Raluy, Laia / Trochimiuk, Magdalena / Appl, Birgit / Heidelbach, Hannah / Vincent, Deirdre / Saleem, Moin A / Reinshagen, Konrad / Mühlig, Anne K / Boettcher, Michael

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 20349

    Abstract: Lithocholic bile acid (LCA) has been reported to selectively kill cancer cells within many tumor cell lines including neuroblastoma or glioblastoma. Wilms' tumor shares similarities with neuro- and glioblastoma. Hence, the aim of the study was to ... ...

    Abstract Lithocholic bile acid (LCA) has been reported to selectively kill cancer cells within many tumor cell lines including neuroblastoma or glioblastoma. Wilms' tumor shares similarities with neuro- and glioblastoma. Hence, the aim of the study was to evaluate the effects of LCA on nephroblastoma. To test the effects of LCA, nephroblastoma cell line WT CLS1 was used. SK NEP1 was tested as well. It was originally classified as a nephroblastoma cell line but was meanwhile reclassified as an ewing sarcoma cell line. As control cell lines HEK 293 from embryonic kidney and RC 124 from adult kidney tissue as well as podocytes were used. The effects were evaluated using proliferation assay, caspase activity assay, FACS and Western blot. LCA showed a dose and time-dependent selective effect inducing apoptosis in nephroblastoma cells. However, these effects were not limited to the nephroblastoma cell line but also affected control kidney cell lines and the sarcoma cells; only podocytes are significantly less affected by LCA (at dosages < 200 µm). There were no significant differences regarding the TGR5 receptor expression. The study showed that LCA has a strong, yet unselective effect on all used in vitro cell-lines, sparing the highly differentiated podocytes in lower concentrations. Further studies are needed to verify our results before dismissing LCA as an anti-cancer drug.
    MeSH term(s) Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis/genetics ; Caspase 3/genetics ; Caspase 3/metabolism ; Caspase 7/genetics ; Caspase 7/metabolism ; Cell Differentiation/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Epithelial Cells/drug effects ; Epithelial Cells/pathology ; Gene Expression Regulation, Neoplastic/drug effects ; HEK293 Cells ; Humans ; Lithocholic Acid/pharmacology ; Podocytes/drug effects ; Podocytes/pathology ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism
    Chemical Substances Antineoplastic Agents ; GPBAR1 protein, human ; Receptors, G-Protein-Coupled ; Lithocholic Acid (5QU0I8393U) ; CASP3 protein, human (EC 3.4.22.-) ; CASP7 protein, human (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Caspase 7 (EC 3.4.22.-)
    Language English
    Publishing date 2020-11-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-77436-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Podocytes Produce and Secrete Functional Complement C3 and Complement Factor H.

    Mühlig, Anne K / Keir, Lindsay S / Abt, Jana C / Heidelbach, Hannah S / Horton, Rachel / Welsh, Gavin I / Meyer-Schwesinger, Catherine / Licht, Christoph / Coward, Richard J / Fester, Lars / Saleem, Moin A / Oh, Jun

    Frontiers in immunology

    2020  Volume 11, Page(s) 1833

    Abstract: Podocytes are an important part of the glomerular filtration barrier and the key player in the development of proteinuria, which is an early feature of complement mediated renal diseases. Complement factors are mainly liver-born and present in ... ...

    Abstract Podocytes are an important part of the glomerular filtration barrier and the key player in the development of proteinuria, which is an early feature of complement mediated renal diseases. Complement factors are mainly liver-born and present in circulation. Nevertheless, there is a growing body of evidence for additional sites of complement protein synthesis, including various cell types in the kidney. We hypothesized that podocytes are able to produce complement components and contribute to the local balance of complement activation and regulation. To investigate the relevant balance between inhibiting and activating sides, our studies focused on complement factor H (CFH), an important complement regulator, and on C3, the early key component for complement activation. We characterized human cultured podocytes for the expression and secretion of activating and regulating complement factors, and analyzed the secretion pathway and functional activity. We studied glomerular CFH and C3 expression in puromycin aminonucleoside (PAN) -treated rats, a model for proteinuria, and the physiological mRNA-expression of both factors in murine kidneys. We found, that C3 and CFH were expressed in cultured podocytes and expression levels differed from those in cultivated glomerular endothelial cells. The process of secretion in podocytes was stimulated with interferon gamma and located in the Golgi apparatus. Cultured podocytes could initiate the complement cascade by the splitting of C3, which can be shown by the generation of C3a, a functional C3 split product. C3 contributed to external complement activation. Podocyte-secreted CFH, in conjunction with factor I, was able to split C3b. Podocytes derived from a patient with a CFH mutation displayed impaired cell surface complement regulation. CFH and C3 were synthesized in podocytes of healthy C57Bl/6-mice and were upregulated in podocytes of PAN treated rats. These data show that podocytes produce functionally active complement components, and could therefore influence the local glomerular complement activation and regulation. This modulating effect should therefore be considered in all diseases where glomerular complement activation occurs. Furthermore, our data indicate a potential novel role of podocytes in the innate immune system.
    MeSH term(s) Animals ; Complement Activation/immunology ; Complement C3/immunology ; Complement C3/metabolism ; Complement Factor H/immunology ; Complement Factor H/metabolism ; Humans ; Male ; Podocytes/immunology ; Podocytes/metabolism ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Complement C3 ; Complement Factor H (80295-65-4)
    Language English
    Publishing date 2020-08-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.01833
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: The calcium-sensing receptor stabilizes podocyte function in proteinuric humans and mice.

    Mühlig, Anne K / Steingröver, Johanna / Heidelbach, Hannah S / Wingerath, Madelaine / Sachs, Wiebke / Hermans-Borgmeyer, Irm / Meyer-Schwesinger, Catherine / Choi, Hoon Young / Lim, Beom Jin / Patry, Christian / Hoffmann, Georg Friedrich / Endlich, Nicole / Bracke, Katharina / Weiß, Mariella / Guse, Andreas H / Lassé, Moritz / Rinschen, Markus M / Braun, Fabian / Huber, Tobias B /
    Puelles, Victor G / Schmitt, Claus Peter / Oh, Jun

    Kidney international

    2022  Volume 101, Issue 6, Page(s) 1186–1199

    Abstract: Calcimimetic agents allosterically increase the calcium ion sensitivity of the calcium-sensing receptor (CaSR), which is expressed in the tubular system and to a lesser extent in podocytes. Activation of this receptor can reduce glomerular proteinuria ... ...

    Abstract Calcimimetic agents allosterically increase the calcium ion sensitivity of the calcium-sensing receptor (CaSR), which is expressed in the tubular system and to a lesser extent in podocytes. Activation of this receptor can reduce glomerular proteinuria and structural damage in proteinuric animal models. However, the precise role of the podocyte CaSR remains unclear. Here, a CaSR knockdown in cultured murine podocytes and a podocyte-specific CaSR knockout in BALB/c mice were generated to study its role in proteinuria and kidney function. Podocyte CaSR knockdown abolished the calcimimetic R-568 mediated calcium ion-influx, disrupted the actin cytoskeleton, and reduced cellular attachment and migration velocity. Adriamycin-induced proteinuria enhanced glomerular CaSR expression in wild-type mice. Albuminuria, podocyte foot process effacement, podocyte loss and glomerular sclerosis were significantly more pronounced in adriamycin-treated podocyte-specific CaSR knockout mice compared to wild-type littermates. Co-treatment of wild-type mice with adriamycin and the calcimimetic cinacalcet reduced proteinuria in wild-type, but not in podocyte-specific CaSR knockout mice. Additionally, four children with nephrotic syndrome, whose parents objected to glucocorticoid therapy, were treated with cinacalcet for one to 33 days. Proteinuria declined transiently by up to 96%, serum albumin increased, and edema resolved. Thus, activation of podocyte CaSR regulates key podocyte functions in vitro and reduced toxin-induced proteinuria and glomerular damage in mice. Hence, our findings suggest a potential novel role of CaSR signaling in control of glomerular disease.
    MeSH term(s) Animals ; Calcium/metabolism ; Cinacalcet/pharmacology ; Cinacalcet/therapeutic use ; Doxorubicin/toxicity ; Humans ; Kidney Diseases/metabolism ; Mice ; Mice, Knockout ; Podocytes/metabolism ; Proteinuria/chemically induced ; Proteinuria/genetics ; Proteinuria/metabolism ; Receptors, Calcium-Sensing/genetics ; Receptors, Calcium-Sensing/metabolism
    Chemical Substances Receptors, Calcium-Sensing ; Doxorubicin (80168379AG) ; Calcium (SY7Q814VUP) ; Cinacalcet (UAZ6V7728S)
    Language English
    Publishing date 2022-03-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2022.01.036
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 797: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top