Ammonia-induced Na,K-ATPase/ouabain-mediated EGF receptor transactivation, MAPK/ERK and PI3K/AKT signaling and ROS formation cause astrocyte swelling

Dai, Huanyun; Song, Dan; Xu, Junnan; Li, Baoman; Hertz, Leif; Peng, Liang

doi:10.1016/j.neuint.2013.09.005

Cited by 55 publications

(41 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylation of ERK, increased ROS production and swelling in ammonia-exposed cultured astrocytes is abolished by the ouabain antagonist canrenone (Fig. 6) [144]. This is consistent with observations in cardiac myocytes that ouabain increases ROS, an effect that was antagonized by a dominant negative Ras, suggesting Ras involvement in ROS generation [189].…”

Section: Cyclic Gmp and Nitric Oxidesupporting

confidence: 87%

“…5) [142,143]. Similarly, Dai et al [144] found an increase in cell volume of cultured astrocytes after 12 h' exposure to 3 mM ammonia. Kelly and Rose [145] showed in hippocampal slices that intracellular Na + in astrocytes but not in neurons rapidly increased by 25-30 mM after exposure to a high concentration of NH 4 Cl (5 mM).…”

Section: Effects Of Hyperammonemia Due To Similarity With Catalytic Amentioning

confidence: 79%

“…This is accompanied by increased expression of the astrocytic α2 subunit of the Na + ,K + -ATPase [185], which is abolished by AG1478, an inhibitor of the epidermal growth factor receptor (EGFR). This receptor is a key component of a pathway mediated by endogenous ouabain(s) in cultured astrocytes [144,152,169]. This astrocytic pathway [169] leads like many other signaling pathways initiated by G-protein-coupled receptors [186,187] to metalloproteinase-mediated release of a growth factor and 'transactivation' and phosphorylation of the EG FR [188].…”

Section: Cyclic Gmp and Nitric Oxidementioning

confidence: 99%

See 2 more Smart Citations

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

et al. 2016

Self Cite

View full text Add to dashboard Cite

Effects of ammonia on astrocytes play a major role in hepatic encephalopathy, acute liver failure and other diseases caused by increased arterial ammonia concentrations (e.g., inborn errors of metabolism, drug or mushroom poisoning). There is a direct correlation between arterial ammonia concentration, brain ammonia level and disease severity. However, the pathophysiology of hyperammonemic diseases is disputed. One long recognized factor is that increased brain ammonia triggers its own detoxification by glutamine formation from glutamate. This is an astrocytic process due to the selective expression of the glutamine synthetase in astrocytes. A possible deleterious effect of the resulting increase in glutamine concentration has repeatedly been discussed and is supported by improvement of some pathologic effects by GS inhibition. However, this procedure also inhibits a large part of astrocytic energy metabolism and may prevent astrocytes from responding to pathogenic factors. A decrease of the already low glutamate concentration in astrocytes due to increased synthesis of glutamine inhibits the malate-aspartate shuttle and energy metabolism. A more recently described pathogenic factor is the resemblance between NH and K in their effects on the Na,K-ATPase and the Na,K, 2 Cl and water transporter NKCC1. Stimulation of the Na,K-ATPase driven NKCC1 in both astrocytes and endothelial cells is essential for the development of brain edema. Na,K-ATPase stimulation also activates production of endogenous ouabains. This leads to oxidative and nitrosative damage and sensitizes NKCC1. Administration of ouabain antagonists may accordingly have therapeutic potential in hyperammonemic diseases.

show abstract

Section: Cyclic Gmp and Nitric Oxidesupporting

confidence: 87%

Section: Effects Of Hyperammonemia Due To Similarity With Catalytic Amentioning

confidence: 79%

Section: Cyclic Gmp and Nitric Oxidementioning

confidence: 99%

See 1 more Smart Citation

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, some cytokines, such as transforming growth factor beta, interleukin-8, and tumor necrosis factor alpha, mediate the secretion of heparin-binding EGF-like growth factor and transforming growth factor a while inducing EGFR activation (Lappano and Maggiolini, 2011;Maillé et al, 2011;Moreno-Càceres et al, 2014). Reactive oxygen species, which are generated by ammonia and angiotensin II, activate EGFR through a nonligand-dependent pathway (Sorkin, 2001;Ding et al, 2007;Dai et al, 2013). Therefore, additional investigations are necessary to clarify these phenomena.…”

Section: Discussionmentioning

confidence: 99%

Induction of Epithelial-Mesenchymal Transition via Activation of Epidermal Growth Factor Receptor Contributes to Sunitinib Resistance in Human Renal Cell Carcinoma Cell Lines

Mizumoto

Yamamoto

Nakayama

et al. 2015

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Sunitinib is widely used for treating renal cell carcinoma (RCC). However, some patients do not respond to treatment with this drug. We aimed to study the association between sunitinib sensitivity and epithelial-mesenchymal transition (EMT) regulation via epidermal growth factor receptor (EGFR) signaling, which is a mechanism of resistance to anticancer drugs. Three RCC cell lines (786-O, ACHN, and Caki-1) were used, and then we evaluated cell viability, EMT regulatory proteins, and signal transduction with sunitinib treatment. Cell viability of 786-O cells was maintained after treatment with sunitinib. After treatment with sunitinib, EGFR phosphorylation increased in 786-O cells, resulting in an increase in the phosphorylation of extracellular signal-regulated kinase, nuclear translocation of b-catenin, and expression of mesenchymal markers. These results suggest that sunitinib induced EMT via activation of EGFR in 786-O cells, but not in ACHN and Caki-1 cells. Caki-1/SN cells, a resistant cell line generated by continuous exposure to sunitinib, displayed increased phosphorylation of EGFR. Cell viability in the presence of sunitinib was decreased by erlotinib, as the selective inhibitor of EGFR, treatment in 786-O and Caki-1/SN cells. Similarly, erlotinib suppressed sunitinib-induced EGFR activation and upregulated mesenchymal markers. Thus, we postulate that resistance to sunitinib in RCC may be associated with EMT caused by activation of EGFR.

show abstract

“…In addition to being directly activated by its cognate ligand, epidermal growth factor (EGF), increasing evidence has revealed that EGFR also serves as a central element in the signal transduction networks activated by other stimuli, including cytokines (9), ammonia (10), H 2 O 2 (11) and G-protein-coupled receptors (12). Currently, this nonclassical EGFR stimulation process is generally termed 'EGFR transactivation' (12 (10,13). Our previous study demonstrated that insufficient RFA promotes hepatoma cell malignancy via the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)/ERK-induced overexpression of vascular endothelial growth factor (VEGF) (6).…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation

et al. 2017

Self Cite

View full text Add to dashboard Cite

Abstract. Our previous study revealed that insufficient radiofrequency ablation (RFA) promotes the malignancy of human hepatocellular carcinoma (HCC) SMMC7721 cells via the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)/extracellular signal-regulated kinase (ERK)-induced overexpression of vascular endothelial growth factor (VEGF). The aims of the present study were to address the involvement of epidermal growth factor receptor (EGFR) transactivation in the enhanced SMMC7721 cell proliferation induced by insufficient RFA, in addition to its association with the CaMKII/ERK/VEGF signaling cascade. SMMC7721 cells were subjected to a 47˚C treatment regimen to simulate insufficient RFA. Cell proliferation was determined using MTT and colony formation assays. The expression levels of VEGF, CaMKII, phosphorylated (phospho)-CaMKII, ERK, phospho-ERK, EGFR and phospho-EGFR were analyzed using western blotting. The results demonstrated that the enhancement of SMMC7721 cell proliferation by the 47˚C treatment regimen was significantly inhibited by exposure of the cells to AG178 (a specific inhibitor of EGFR). Furthermore, AG1478 exposure prevented the overexpression of VEGF and phosphorylation of ERK, but had no significant effects on CaMKII phosphorylation. By contrast, 47˚C treatment-induced EGFR phosphorylation was inhibited by treatment with KN93 (a specific inhibitor of CaMKII). Overall, the results of the present study have suggested a role for EGFR transactivation in the RFA-promoted growth of residual HCC. Thus, targeting EGFR may represent a useful preventive and therapeutic strategy for RFA-induced HCC progression and recurrence.

show abstract

Ammonia-induced Na,K-ATPase/ouabain-mediated EGF receptor transactivation, MAPK/ERK and PI3K/AKT signaling and ROS formation cause astrocyte swelling

Cited by 55 publications

References 103 publications

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity

Induction of Epithelial-Mesenchymal Transition via Activation of Epidermal Growth Factor Receptor Contributes to Sunitinib Resistance in Human Renal Cell Carcinoma Cell Lines

Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation

Contact Info

Product

Resources

About