Targeting Na/K-ATPase Signaling: A New Approach to Control Oxidative Stress

Liu, Jiang; Lilly, Megan N.; Shapiro, Joseph I.

doi:10.2174/1381612824666180110101052

Cited by 38 publications

(24 citation statements)

References 84 publications

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“…The advent of the discovery of the scaffolding and signaling functions of the NKA (Na + /K + -ATPase) twenty years ago by Xie and Askari has opened up a multitude of newly appreciated roles for the NKA in both health and disease in almost every major organ system [ 1 , 2 , 3 ]. Whereas a number of recent reviews have focused on new insights into sodium handling and other physiologically relevant processes directed by NKA signaling [ 4 , 5 , 6 , 7 , 8 , 9 ], in the current review we will examine the evidence for some of the long-term “trade-offs” of these physiological processes which were originally proposed by Neal Bricker in 1972 [ 10 ] ( Figure 1 ). This includes the NKA’s role in inflammation and fibrosis in target organs including the heart, kidney, and vasculature.…”

Section: Introductionmentioning

confidence: 99%

“…This review will also highlight the recent developments in what is known about mechanisms of trade-off pathways as they related to CTS-NKA-Src (cardiotonic steroids- Na + /K + -ATPase-Src kinase) signaling. Recent findings [ 5 , 11 , 12 , 13 ], which include the mechanism by which CTS, NKA ligands, can signal through the NKA α-1, have increased the interest in this area significantly. This article will also highlight new developments in what is known about molecular partners of the NKA which help mediate these trade-off pathways.…”

Section: Introductionmentioning

confidence: 99%

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Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na+/K+-ATPase

Khalaf

Dube

Mohamed

et al. 2018

IJMS

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In 1972 Neal Bricker presented the “trade-off” hypothesis in which he detailed the role of physiological adaptation processes in mediating some of the pathophysiology associated with declines in renal function. In the late 1990’s Xie and Askari published seminal studies indicating that the Na+/K+-ATPase (NKA) was not only an ion pump, but also a signal transducer that interacts with several signaling partners. Since this discovery, numerous studies from multiple laboratories have shown that the NKA is a central player in mediating some of these long-term “trade-offs” of the physiological adaptation processes which Bricker originally proposed in the 1970’s. In fact, NKA ligands such as cardiotonic steroids (CTS), have been shown to signal through NKA, and consequently been implicated in mediating both adaptive and maladaptive responses to volume overload such as fibrosis and oxidative stress. In this review we will emphasize the role the NKA plays in this “trade-off” with respect to CTS signaling and its implication in inflammation and fibrosis in target organs including the heart, kidney, and vasculature. As inflammation and fibrosis exhibit key roles in the pathogenesis of a number of clinical disorders such as chronic kidney disease, heart failure, atherosclerosis, obesity, preeclampsia, and aging, this review will also highlight the role of newly discovered NKA signaling partners in mediating some of these conditions.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na+/K+-ATPase

Khalaf

Dube

Mohamed

et al. 2018

IJMS

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“…For instance, care has to be taken employing the pNaKtide peptide to target the stria vascularis as the protein acts as an agonist modifying Na/K-ATPase-mediated amplification of ROS signaling [48,109]. This concern of altered cellular function has previously been demonstrated where analogs of NGF bind TrkA and inhibit neurite outgrowth [66].…”

Section: Discussionmentioning

confidence: 99%

Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

Naples

Miller

Ramsey

et al. 2019

Drug Deliv. and Transl. Res.

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The delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cellspecific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targetedinner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults.

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“…It is also responsible for initiating cellular signalling processes that involve reactive oxygen species, important in several pathologies. The inhibition and the onset of the signalling function of Na + / K + -ATPase caused by the interaction with cardiotonic glycosides which bind on the α-subunit of the enzyme classically known [28,46]. In addition, it is also known and documented that different components from frog poisons have antineoplastic activities and actions on the central nervous system due to their effects on Na + /K + -ATPase [7].…”

Section: Discussionmentioning

confidence: 99%

Assessment of neuropharmacological potential of low molecular weight components extracted from Rhinella schneideri toad poison

Baldo

Cunha

Godoy

et al. 2019

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na + /K +-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri toad poison on Na + /K +-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest. Methods: Rhinella schneideri toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at-20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na + /K + ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5 to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent.

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Targeting Na/K-ATPase Signaling: A New Approach to Control Oxidative Stress

Cited by 38 publications

References 84 publications

Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na+/K+-ATPase

Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na+/K+-ATPase

Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

Assessment of neuropharmacological potential of low molecular weight components extracted from Rhinella schneideri toad poison

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