Identification of Na+/K+-ATPase α/β isoforms in Rhinella marina tissues by RNAseq and a molecular docking approach at the protein level to evaluate α isoform affinities for bufadienolides

Medina-Ortiz, Katherine; López-Álvarez, Diana; Navia, Felipe; Hansen, Thomas; Fierro, Leonardo; Castaño, Santiago

doi:10.1016/j.cbpa.2021.110906

Cited by 4 publications

(3 citation statements)

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“…3A ). CGs are known to exert their action primarily by binding to the α-subunit of the Na + /K + ATPase (NKA) pump and inhibiting the intake of K + coupled with the release of Na + out of the cell ( 35 , 36 ). As changes in intracellular ion concentrations can affect the resting membrane potential, the resting membrane potential of HepG2 cells treated with PPM was assessed.…”

Section: Resultsmentioning

confidence: 99%

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

et al. 2023

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Cardiac glycosides (CGs) are candidate anticancer agents that function by increasing [Ca 2+ ]i to induce apoptotic cell death in several types of cancer cells. However, new findings have shown that the anti-cancer effects of CGs involve complex cell-signal transduction mechanisms. Hence, exploring the potential mechanisms of action of CGs may provide insight into their anti-cancer effects and thus aid in the selection of the appropriate CG. Periplocymarin (PPM), which is a cardiac glycoside, is an active ingredient extracted from Cortex periplocae. The role of PPM was evaluated in HepG2 cells and xenografted nude mice. Cell proliferation, real-time ATP rate assays, western blotting, cell apoptosis assays, short interfering RNA transfection, the patch clamp technique, electron microscopy, JC-1 staining, immunofluorescence staining and autophagic flux assays were performed to evaluate the function and regulatory mechanisms of PPM in vitro . The in vivo activity of the PPM was assessed using a mouse xenograft model. The present study demonstrated that PPM synchronously activated lethal apoptosis and protective autophagy in liver cancer, and the initiation of autophagy counteracted the inherent pro-apoptotic capacity and impaired the anti-cancer effects. Specifically, PPM exerted a proapoptotic effect in HepG2 cells and activated macroautophagy by initiation of the AMPK/ULK1 and mTOR signaling pathways. Activation of macroautophagy counteracted the pro-apoptotic effects of PPM, but when it was combined with an autophagy inhibitor, the anti-cancer effects of PPM in mice bearing HepG2 xenografts were observed. Collectively, these results indicated that a self-limiting effect impaired the pro-apoptotic effects of PPM in liver cancer, but when combined with an autophagy inhibitor, it may serve as a novel therapeutic option for the management of liver cancer.

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Section: Resultsmentioning

confidence: 99%

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

et al. 2023

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“…Four isotypes of α subunit (α 1 , α 2 , α 3 , α 4 ) and four isotypes of β subunit (β 1 , β 2 , β 3 , β 4 ) have been identified (Kaplan, 2002). Both α and β subunits are closely related to the functional activity of NKA, but each type of CTS binds and inhibits the α subunit of NKA (McDonough et al, 1990;Medina-Ortiz et al, 2021). The sodium-calcium exchanger (NCX) is a calcium transport system that controls intracellular calcium levels.…”

Section: Study On the Role Of Cts On Heart Failurementioning

confidence: 99%

Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids

et al. 2022

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Cardiotonic steroids (CTS) are a group of compounds existing in animals and plants. CTS are commonly referred to cardiac glycosides (CGs) which are composed of sugar residues, unsaturated lactone rings and steroid cores. Their traditional mechanism of action is to inhibit sodium-potassium ATPase to strengthen the heart and regulate heart rate, so it is currently widely used in the treatment of cardiovascular diseases such as heart failure and tachyarrhythmia. It is worth noticing that recent studies have found an avalanche of inestimable values of CTS applications in many fields such as anti-tumor, anti-virus, neuroprotection, and immune regulation through multi-molecular mechanisms. Thus, the pharmacological activities and applications of CTS have extensive prospects, which would provide a direction for new drug research and development. Here, we review the potential applications of CTS in cardiovascular system and other systems. We also provide suggestions for new clinical practical strategies of CTS, for many diseases. Four main themes will be discussed, in relation to the impact of CTS, on 1) tumors, 2) viral infections, 3) nervous system diseases and 4) immune-inflammation-related diseases.

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“…Buckard et al (2015) analyzed the role of ATP1A1 in signal transduction involving cardiotonic binding induced signals through an Src signaling mediated pathway [ 34 ]. The cardiotonic steroids digoxin, ouabain, and bufarin act as specific inhibitors of ATP1A1 [ 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative Expression Profiling and Sequence Characterization of ATP1A1 Gene Associated with Heat Tolerance in Tropically Adapted Cattle

Elayadeth-Meethal

Veettil

Asaf

et al. 2021

Animals

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Climate change is an imminent threat to livestock production. One adaptation strategy is selection for heat tolerance. While it is established that the ATP1A1 gene and its product play an important role in the response to many stressors, there has been no attempt to characterize the sequence or to perform expression profiling of the gene in production animals. We undertook a field experiment to compare the expression profiles of ATP1A1 in heat-tolerant Vechur and Kasaragod cattle (Bos taurus indicus) with the profile of a heat-susceptible crossbreed (B. t. taurus × B. t. indicus). The cattle were exposed to heat stress while on pasture in the hot summer season. The environmental stress was quantified using the temperature humidity index (THI), while the heat tolerance of each breed was assessed using a heat tolerance coefficient (HTC). The ATP1A1 mRNA of Vechur cattle was amplified from cDNA and sequenced. The HTC varied significantly between the breeds and with time-of-day (p < 0.01). The breed–time-of-day interaction was also significant (p < 0.01). The relative expression of ATP1A1 differed between heat-tolerant and heat-susceptible breeds (p = 0.02). The expression of ATP1A1 at 08:00, 10:00 and 12:00, and the breed–time-of-day interaction, were not significant. The nucleotide sequence of Vechur ATP1A1 showed 99% homology with the B. t. taurus sequence. The protein sequence showed 98% homology with B. t. taurus cattle and with B. grunniens (yak) and 97.7% homology with Ovis aries (sheep). A molecular clock analysis revealed evidence of divergent adaptive evolution of the ATP1A1 gene favoring climate resilience in Vechur cattle. These findings further our knowledge of the relationship between the ATP1A1 gene and heat tolerance in phenotypically incongruent animals. We propose that ATP1A1 could be used in marker assisted selection (MAS) for heat tolerance.

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Identification of Na+/K+-ATPase α/β isoforms in Rhinella marina tissues by RNAseq and a molecular docking approach at the protein level to evaluate α isoform affinities for bufadienolides

Cited by 4 publications

References 65 publications

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

Dual targets of lethal apoptosis and protective autophagy in liver cancer with periplocymarin elicit a limited therapeutic effect

Research Progress in Pharmacological Activities and Applications of Cardiotonic Steroids

Comparative Expression Profiling and Sequence Characterization of ATP1A1 Gene Associated with Heat Tolerance in Tropically Adapted Cattle

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