GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    The cardiotonic steroid hormone marinobufagenin induces renal fibrosis: implication of epithelial-to-mesenchymal transition
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Renal Physiology Vol. 296, No. 4 ( 2009-04), p. F922-F934
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 296, No. 4 ( 2009-04), p. F922-F934
    Abstract: We recently demonstrated that the cardiotonic steroid marinobufagenin (MBG) induced fibrosis in rat hearts through direct stimulation of collagen I secretion by cardiac fibroblasts. This stimulation was also responsible for the cardiac fibrosis seen in experimental renal failure. In this study, the effect of MBG on the development of renal fibrosis in rats was investigated. Four weeks of MBG infusion triggered mild periglomerular and peritubular fibrosis in the cortex and the appearance of fibrotic scars in the corticomedullary junction of the kidney. MBG also significantly increased the protein levels and nuclear localization of the transcription factor Snail in the tubular epithelia. It is known that activation of Snail is associated with epithelial-to-mesenchymal transition (EMT) during renal fibrosis. To examine whether MBG alone can trigger EMT, we used the porcine proximal tubular cell line LLC-PK1. MBG (100 nM) caused LLC-PK1 cells grown to confluence to acquire a fibroblast-like shape and have an invasive motility. The expressions of the mesenchymal proteins collagen I, fibronectin, and vimentin were increased twofold. However, the total level of E-cadherin remained unchanged. These alterations in LLC-PK1 cells in the presence of MBG were accompanied by elevated expression and nuclear translocation of Snail. During the time course of EMT, MBG did not have measurable inhibitory effects on the ion pumping activity of its natural ligand, Na + -K + -ATPase. Our data suggest that the MBG may be an important factor in inducing EMT and, through this mechanism, elevated levels of MBG in chronic renal failure may play a role in the progressive fibrosis.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.90605.2008
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Renal Physiology Vol. 296, No. 5 ( 2009-05), p. F1219-F1226
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 296, No. 5 ( 2009-05), p. F1219-F1226
    Abstract: The cardiotonic steroid marinobufagenin (MBG) has been implicated in the pathogenesis of experimental uremic cardiomyopathy, which is characterized by progressive cardiac fibrosis. We examined whether the transcription factor Friend leukemia integration-1 (Fli-1) might be involved in this process. Fli-1-knockdown mice demonstrated greater cardiac collagen-1 expression and fibrosis compared with wild-type mice; both developed increased cardiac collagen expression and fibrosis after 5/6 nephrectomy. There was a strong inverse relationship between the expressions of Fli-1 and procollagen in primary culture of rat cardiac and human dermal fibroblasts as well as a cell line derived from renal fibroblasts and MBG-induced decreases in nuclear Fli-1 as well as increases in procollagen-1 expression in these cells. Transfection of a Fli-1 expression vector prevented increased procollagen-1 expression from MBG. MBG exposure induced a rapid translocation of the δ-isoform of protein kinase C (PKCδ) to the nucleus. This translocation was prevented by pharmacological inhibition of phospholipase C, and MBG-induced increases in procollagen-1 expression were prevented with a PKCδ- but not a PKCα-specific inhibitor. Finally, immunoprecipitation studies strongly suggest that MBG induced phosphorylation of Fli-1. We feel these data support a causal relationship with MBG-induced translocation of PKCδ, which results in phosphorylation of as well as decreases in nuclear Fli-1 expression, which, in turn, leads to increases in collagen production. Should these findings be confirmed, we speculate that this pathway may represent a therapeutic target for uremic cardiomyopathy as well as other conditions associated with excessive fibrosis.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.90710.2008
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 294, No. 4 ( 2008-04), p. R1248-R1254
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 294, No. 4 ( 2008-04), p. R1248-R1254
    Abstract: Factors that mediate increases in salt sensitivity of blood pressure with age remain to be clarified. The present study investigated 1) the effects of high-NaCl intake on two Na pump inhibitors, endogenous ouabain (EO) and marinobufagenin (MBG), in middle-aged and older normotensive Caucasian women; and 2) whether individual differences in EO and MBG are linked to variations in sodium excretion or salt sensitivity. A change from 6 days of a lower (0.7 mmol·kg −1 ·day −1 )- to 6 days of a higher (4 mmol·kg −1 ·day −1 )-NaCl diet elicited a sustained increase in MBG excretion that directly correlated with an increase in the fractional Na excretion and was inversely related to age and to an age-dependent increase in salt sensitivity. In contrast, EO excretion increased only transiently in response to NaCl loading and did not vary with age or correlate with fractional Na excretion or salt sensitivity. A positive correlation of both plasma and urine levels of EO and MBG during salt loading may indicate a casual link between two Na pump inhibitors in response to NaCl loading, as observed in animal models. A linear mixed-effects model demonstrated that age, dietary NaCl, renal MBG excretion, and body mass index were each independently associated with systolic blood pressure. Thus, a sustained increase in MBG in response to acutely elevated dietary NaCl is inversely linked to salt sensitivity in normotensive middle-aged and older women, and a relative failure of MBG elaboration by these older persons may be involved in the increased salt sensitivity with advancing age.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.00782.2007
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477297-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Interaction of NaCl and behavioral stress on endogenous sodium pump ligands in rats
    American Physiological Society ; 2001
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 281, No. 1 ( 2001-07-01), p. R352-R358
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 281, No. 1 ( 2001-07-01), p. R352-R358
    Abstract: Our study investigated the hypothesis that the combination of a high NaCl diet and social isolation stress would increase systolic blood pressure (SBP) and endogenous sodium pump ligands (SPL), ouabainlike compound (OLC), and marinobufagenin (MBG). Excretion of MBG and OLC, SBP, and organ weights were studied in four groups ( n = 8) of male Fisher 344 × Norwegian brown rats: controls, socially isolated (Iso), 4% NaCl diet (Salt), and the combination of Salt and Iso (Iso+Salt). In Salt, MBG excretion increased by 78% ( P 〈 0.01), whereas SBP and OLC remained unchanged. In Iso, SBP and MBG did not change, but OLC peaked on day 1. In the Iso+Salt, SBP increased by 9 mmHg, MBG excretion increased (42.0 ± 7.6 vs. 10.0 ± 1.5 pmol/24 h, P 〈 0.01), whereas OLC peaked at day 1(25.0 ± 2.5 vs. 10.0 ± 2.0 pmol/24 h, P 〈 0.01) and remained elevated. Heart and kidney weights were increased in Salt and Iso+Salt. Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.2001.281.1.R352
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2001
    detail.hit.zdb_id: 1477297-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Partial nephrectomy as a model for uremic cardiomyopathy in the mouse
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Renal Physiology Vol. 294, No. 2 ( 2008-02), p. F450-F454
    Details
    In: American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 294, No. 2 ( 2008-02), p. F450-F454
    Abstract: Because of the plethora of genetic manipulations available in the mouse, we performed a partial nephrectomy in the mouse and examined whether the phenotypical features of uremic cardiomyopathy described in humans and rats were also present in the murine model. A nephrectomy was performed using a combination of electrocautory to decrease renal mass on the left kidney and right surgical nephrectomy. This procedure produced substantial and persistent hypertension as well as increases in circulating concentrations of marinobufagenin. Invasive physiological measurements of cardiac function demonstrated that the nephrectomy resulted in impairment of both active and passive left ventricular relaxation at 4 wk whereas tissue Doppler imaging detected changes in diastolic function after 6 wk. Morphologically, hearts demonstrated enlargement and progressive fibrosis, and biochemical measurements demonstrated downregulation of the sarcoplasmic reticulum calcium ATPase as well as increases in collagen-1, fibronectin, and vimentin expression. Our results suggest that partial nephrectomy in the mouse establishes a model of uremic cardiomyopathy which shares phenotypical features with the rat model as well as patients with chronic renal failure.
    Type of Medium: Online Resource
    ISSN: 1931-857X , 1522-1466
    URL: Article
    DOI: 10.1152/ajprenal.00472.2007
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477287-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Marinobufagenin enhances cardiac contractility in mice with ouabain-sensitive α 1 Na + -K + -ATPase
    American Physiological Society ; 2009
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 296, No. 6 ( 2009-06), p. H1833-H1839
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 296, No. 6 ( 2009-06), p. H1833-H1839
    Abstract: Endogenous Na + pump inhibitors are thought to play important (patho)physiological roles and occur in two different chemical forms in the mammalian circulation: cardenolides, such as ouabain, and bufadienolides, such as marinobufagenin (MBG). Although all α Na + -K + -ATPase isoforms (α 1-4 ) are sensitive to ouabain in most species, in rats and mice the ubiquitously expressed α 1 Na + -K + -ATPase is resistant to ouabain. We have previously shown that selective modification of the putative ouabain binding site of either the α 1 or α 2 Na + -K + -ATPase subunit in mice substantially alters the cardiotonic influence of exogenously applied cardenolides. To determine whether the ouabain binding site also interacts with MBG and if this interaction plays a functional role, we evaluated cardiovascular function in α 1 -resistant/α 2 -resistant (α 1 R/R α 2 R/R ), α 1 -sensitive/α 2 -resistant (α 1 S/S α 2 R/R ), and α 1 -resistant/α 2 -sensitive mice (α 1 R/R α 2 S/S , wild type). Cardiovascular indexes were evaluated in vivo by cardiac catheterization at baseline and during graded infusions of MBG. There were no differences in baseline measurements of targeted mice, indicating normal hemodynamics and cardiac function. MBG at 0.025, 0.05, and 0.1 nmol·min −1 ·g body wt −1 significantly increased cardiac performance to a greater extent in α 1 S/S α 2 R/R compared with α 1 R/R α 2 R/R and wild-type mice. The increase in LVdP/d t max in α 1 S/S α 2 R/R mice was greater at higher concentrations of MBG compared with both α 1 R/R α 2 R/R and α 1 R/R α 2 S/S mice ( P 〈 0.05). These results suggest that MBG interacts with the ouabain binding site of the α 1 Na + -K + -ATPase subunit and can thereby influence cardiac inotropy.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00285.2009
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2009
    detail.hit.zdb_id: 1477308-9
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...