Protein Interaction and Na/K-ATPase-Mediated Signal Transduction

Cui, Xiaoyu; Xie, Zijian

doi:10.3390/molecules22060990

Cited by 118 publications

(68 citation statements)

References 183 publications

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“…While it is not known if the IC 50 for the Na/K-ATPase pump inhibition can reflect the binding capability of CTS with the Na/K-ATPase as the receptor and at which concentration the receptor binding sites will be saturated with digitoxigenin, the lower IC 50 value for digitoxigenin (0.22 µM) than for digoxin (1.76 µM) (unpublished data) might suggest that the saturation would occur at a lower concentration of digitoxigenin. The unobserved dose-dependent response might be also related to the large data variability and the possible involvement of other signal transductions to stimulate collagen synthesis in HDF following exposure to digitoxigenin [15]. …”

Section: Discussionmentioning

confidence: 99%

Topical Digitoxigenin for Wound Healing: A Feasibility Study

Feng

Wang

et al. 2018

Bioengineering

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(1) Background: Cardiotonic steroids have been found to stimulate collagen synthesis and might be potential wound healing therapeutics. The objective of this study was to evaluate the feasibility of digitoxigenin and its topical formulation for wound healing; (2) Methods: In the in vitro study, the human dermal fibroblast cells were treated with digitoxigenin and collagen synthesis was assessed. In the in vivo study, digitoxigenin was applied to excisional full-thickness wounds in rats immediately after wounding and remained for three days, and wound open was evaluated over 10 days. A digitoxigenin formulation for topical administration was prepared, and the in vitro release and in vivo wound healing effect were investigated; (3) Results: The expression of procollagen in human dermal fibroblast was significantly increased with the exposure to 0.1 nM digitoxigenin. Topical application of digitoxigenin in olive oil or alginate solution for three days significantly decreased the wound open in rats. Similarly, topical administration of the developed digitoxigenin formulation for three days also significantly increased wound healing. No wound healing effects were observed at days 7 and 10 after wounding when digitoxigenin was not applied; and, (4) Conclusions: It was possible to deliver digitoxigenin using the developed formulation. However, the wound healing effect of digitoxigenin and its mechanisms need to be further investigated in future studies.

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Section: Discussionmentioning

confidence: 99%

Topical Digitoxigenin for Wound Healing: A Feasibility Study

Feng

Wang

et al. 2018

Bioengineering

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“…In cardiac myocytes, CTS induce an increase of intracellular Na + , which leads to the accumulation of intracellular Ca 2+ through functional coupling to the Na + /Ca 2+ exchanger (NCX) stimulating contractility [155]. Since CTS concentrations much lower than Na, K-ATPase IC 50 were recognized a long time ago to stimulate growth-linked pathways, the Na, K-ATPase is suspected to have functions independent on its pump activity [156]. Besides the control of ionic concentrations, it is now wellaccepted that the Na, K-ATPase plays a key role in cellular signal transduction through both direct interactions with signaling proteins and its ability to organize specific membrane microdomains [156].…”

Section: The Na K-atpase and Sarco(endo)-plasmic Ca-atpase Regulatedmentioning

confidence: 99%

Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders

Gianfrancesco

Paquot

Piette

et al. 2018

Biochemical Pharmacology

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The maintenance of the characteristic lipid compositions and physicochemical properties of biological membranes is essential for their proper function. Mechanisms allowing to sense and restore membrane homeostasis have been identified in prokaryotes for a long time and more recently in eukaryotes. A membrane remodeling can result from aberrant metabolism as seen in obesity. In this review, we describe how such lipid bilayer stress can account for the modulation of membrane proteins involved in the pathogenesis of obesity-linked inflammatory and metabolic disorders. We address the case of the Toll-like receptor 4 that is implicated in the obesity-related low grade inflammation and insulin resistance. The lipid raft-mediated TLR4 activation is promoted by an enrichment of the plasma membrane with saturated lipids or cholesterol increasing the lipid phase order. We discuss of the plasma membrane Na, K-ATPase that illustrates a new concept according to which direct interactions between specific residues and particular lipids determine both stability and activity of the pump in parallel with indirect effects of the lipid bilayer. The closely related sarco(endo)-plasmic Ca-ATPase embedded in the more fluid ER membrane seems to be more sensitive to a lipid bilayer stress as demonstrated by its inactivation in cholesterol-loaded macrophages or its inhibition mediated by an increased PtdCho/PtdEtn ratio in obese mice hepatocytes. Finally, we describe the model recently proposed for the activation of the conserved IRE-1 protein through alterations in the ER membrane lipid packing and thickness. Such IRE-1 activation could occur in response to abnormal lipid synthesis and membrane remodeling as observed in hepatocytes exposed to excess nutrients. Since the IRE-1/XBP1 branch also stimulates the lipid synthesis, this pathway could create a vicious cycle "lipogenesis-ER lipid bilayer stress-lipogenesis" amplifying hepatic ER pathology and the obesity-linked systemic metabolic defects.

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“…We suggested that the ion-transport-independent Src signalling pathway, which is modulated by the Na + ,K + -ATPase (Cui & Xie, 2017), plays an important role in the regulation of brain perfusion in normal conditions and in pathologies, including FHM2. We suggest that Src activity, which is normally suppressed by the Na + ,K + -ATPase, is activated upon FHM2-associated knockdown of the 2 isoform in cerebral arteries .…”

Section: Resultsmentioning

confidence: 99%

“…Involvement of vascular Na + ,K + -ATPase in signal transduction that does not depend directly on ion transport was previously suggested (Zulian et al, 2013). This mechanism has been characterized in nonvascular tissues and involves an interaction of the Na + ,K + -ATPase with a number of signalling molecules, including Src kinase (Cui & Xie, 2017). Src was shown to be activated by autophosphorylation upon binding of some cardiotonic steroids, including ouabain, to the Na + ,K + -ATPase.…”

Section: Ion-transport-independent Signal Transductionmentioning

confidence: 95%

“…At present, there is no consensus regarding the mechanism for Src activation. There is substantial evidence for physical interaction between the Na + ,K + -ATPase and Src that is disturbed by ouabain but does not depend on ATPase activity (for details, see Cui & Xie, 2017). This is in disagreement with cell-free assay-based studies, which suggested that Src is activated by changes in ATP consumption (Yosef, Katz, Peleg, Mehlman, & Karlish, 2016).…”

Section: Ion-transport-independent Signal Transductionmentioning

confidence: 99%

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Involvement of the Na⁺,K⁺‐ATPase isoforms in control of cerebral perfusion

Staehr

Rajanathan

Matchkov

2019

Experimental Physiology

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New Findings What is the topic of this review?In this review, we consider the role of the Na+,K+‐ATPase in cerebrovascular function and how it might be changed in familial hemiplegic migraine type 2 (FHM2). The primary focus is involvement of the Na+,K+‐ATPase isoforms in regulation of cerebrovascular tone. What advances does it highlight?In this review, we discuss three overall distinct mechanisms whereby the Na+,K+‐ATPase might be capable of regulating cerebrovascular tone. Furthermore, we discuss how changes in the Na+,K+‐ATPase in cerebral arteries might affect brain perfusion and thereby be involved in the pathology of FHM2. Abstract Familial hemiplegic migraine type 2 (FHM2) has been characterized by biphasic changes in cerebral blood flow during a migraine attack, with initial hypoperfusion followed by abnormal hyperperfusion of the affected hemisphere. We suggested that FHM2‐associated loss‐of‐function mutation(s) in the Na+,K+‐ATPase α2 isoform might be responsible for these biphasic changes in several ways. We found that reduced expression of the α2 isoform leads to sensitization of the contractile machinery to [Ca2+]i via Src kinase‐dependent signal transduction. This change in sensitivity might be the underlying mechanism for both abnormally potentiated vasoconstriction and exaggerated vasorelaxation. Moreover, the functional significance of the Na+,K+‐ATPase α2 isoform in astrocytes provides for the possibility of elevated extracellular potassium signalling from astrocytic endfeet to the vascular wall in neurovascular coupling.

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Protein Interaction and Na/K-ATPase-Mediated Signal Transduction

Cited by 118 publications

References 183 publications

Topical Digitoxigenin for Wound Healing: A Feasibility Study

Topical Digitoxigenin for Wound Healing: A Feasibility Study

Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders

Involvement of the Na⁺,K⁺‐ATPase isoforms in control of cerebral perfusion

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Protein Interaction and Na/K-ATPase-Mediated Signal Transduction

Cited by 118 publications

References 183 publications

Topical Digitoxigenin for Wound Healing: A Feasibility Study

Topical Digitoxigenin for Wound Healing: A Feasibility Study

Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders

Involvement of the Na+,K+‐ATPase isoforms in control of cerebral perfusion

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Product

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Involvement of the Na⁺,K⁺‐ATPase isoforms in control of cerebral perfusion