Ouabain inhibits p38 activation in thymocytes

Rodrigues‐Mascarenhas, Sandra; Bloise, Flávia Fonseca; Moscat, Jorge; Rumjanek, Vivian M.

doi:10.1016/j.cellbi.2008.07.012

Cited by 21 publications

(21 citation statements)

References 22 publications

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“…Additionally, we have seen increased p38 phosphorylation caused by ouabain which has been shown earlier in other cell types including COS7 cell line and renal epithelium of the distal tubules (C7‐MDCK) . At the same time, there are data showing p38 deactivation by ouabain in thymocytes . We have shown JNK dephosphorylation after 6 or more hours of incubation with 1‐μM ouabain.…”

Section: Discussionsupporting

confidence: 82%

Ouabain‐induced changes in MAP kinase phosphorylation in primary culture of rat cerebellar cells

Лопачев

Lopacheva

Osipova

et al. 2016

Cell Biochemistry & Function

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Cardiotonic steroid (CTS) ouabain is a well-established inhibitor of Na,K-ATPase capable of inducing signalling processes including changes in the activity of the mitogen activated protein kinases (MAPK) in various cell types. With increasing evidence of endogenous CTS in the blood and cerebrospinal fluid, it is of particular interest to study ouabain-induced signalling in neurons, especially the activation of MAPK, because they are the key kinases activated in response to extracellular signals and regulating cell survival, proliferation and apoptosis. In this study we investigated the effect of ouabain on the level of phosphorylation of three MAPK (ERK1/2, JNK and p38) and on cell survival in the primary culture of rat cerebellar cells. Using Western blotting we described the time course and concentration dependence of phosphorylation for ERK1/2, JNK and p38 in response to ouabain. We discovered that ouabain at a concentration of 1 μM does not cause cell death in cultured neurons while it changes the phosphorylation level of the three MAPK: ERK1/2 is phosphorylated transiently, p38 shows sustained phosphorylation, and JNK is dephosphorylated after a long-term incubation. We showed that ERK1/2 phosphorylation increase does not depend on ouabain-induced calcium increase and p38 activation. Changes in p38 phosphorylation, which is independent from ERK1/2 activation, are calcium dependent. Changes in JNK phosphorylation are calcium dependent and also depend on ERK1/2 and p38 activation. Ten-micromolar ouabain leads to cell death, and we conclude that different effects of 1-μM and 10-μM ouabain depend on different ERK1/2 and p38 phosphorylation profiles. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionsupporting

confidence: 82%

Ouabain‐induced changes in MAP kinase phosphorylation in primary culture of rat cerebellar cells

Лопачев

Lopacheva

Osipova

et al. 2016

Cell Biochemistry & Function

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“…Several lines of evidence have demonstrated that the effect of ouabain on p38 MAPK phosphorylation is cell-type specific [36,55]. We observed here that ouabain was able to induce p38 MAPK activation in lung epithelial cells.…”

Section: Discussionsupporting

confidence: 62%

Involvement of Na+, K+-ATPase and its inhibitors in HuR-mediated cytokine mRNA stabilization in lung epithelial cells

Chen

Cao

et al. 2010

Cell. Mol. Life Sci.

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Increasing evidence demonstrates that Na(+), K(+)-ATPase plays an important role in pulmonary inflammation, but the mechanism remains largely unknown. In this study, we used cardiotonic steroids as Na(+), K(+)-ATPase inhibitors to explore the possible involvement of Na(+), K(+)-ATPase in pulmonary epithelial inflammation. The results demonstrated that mice after ouabain inhalation developed cyclooxygenase-2-dependent acute lung inflammation. The in vitro experiments further confirmed that Na(+), K(+)-ATPase inhibitors significantly stimulated cyclooxygenase-2 expression in lung epithelial cells of human or murine origin, the process of which was participated by multiple cis-elements and trans-acting factors. Most importantly, we first described here that Na(+), K(+)-ATPase inhibitors could evoke a significant Hu antigen R nuclear export in lung epithelial cells, which stabilized cyclooxygenase-2 mRNA by binding with a proximal AU-rich element within its 3'-untranslated region. In conclusion, HuR-mediated mRNA stabilization opens new avenues in understanding the importance of Na(+), K(+)-ATPase, as well as its inhibitors in inflammation.

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“…Recent studies have demonstrated a relationship among cardiac glycosides, PKCδ, and mitogen-activated protein kinases (MAPKs)2627. Our results showed that lanatoside C decreased phosphorylation of the MAPK, ERK1/2 (extracellular signal-regulated kinase 1/2), but not that of c-Jun N-terminal kinase (JNK) or p38, in Hep3B and HA22T cells, and did so in a concentration-dependent manner; it also exerted a sustained, time-dependent inhibitory effect on ERK1/2 phosphorylation in Hep3B cells (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells

Chao

Chen

Huang

et al. 2017

Sci Rep

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Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss. Moreover, lanatoside C triggered mitochondrial membrane potential (MMP) loss, activation of caspases and translocation of apoptosis-inducing factor (AIF) into the nucleus, which suggests that lanatoside C induced apoptosis through both caspase-dependent and -independent pathways. Furthermore, we discovered that lanatoside C activated protein kinase delta (PKCδ) via Thr505 phosphorylation and subsequent membrane translocation. Inhibition of PKCδ reversed lanatoside C-induced MMP loss and apoptosis, confirming that lanatoside C caused apoptosis through PKCδ activation. We also found that the AKT/mTOR pathway was negatively regulated by lanatoside C through PKCδ activation. In conclusion, we provide the first demonstration that the anticancer effects of lanatoside C are mainly attributable to PKCδ activation.

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Ouabain inhibits p38 activation in thymocytes

Cited by 21 publications

References 22 publications

Ouabain‐induced changes in MAP kinase phosphorylation in primary culture of rat cerebellar cells

Ouabain‐induced changes in MAP kinase phosphorylation in primary culture of rat cerebellar cells

Involvement of Na+, K+-ATPase and its inhibitors in HuR-mediated cytokine mRNA stabilization in lung epithelial cells

Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells

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