Na/K-ATPase under Oxidative Stress: Molecular Mechanisms of Injury

Dobrota, Dušan; Matejovičová, Milena; Kurella, Ekaterina G.; Boldyrev, Alexander A.

doi:10.1023/a:1006928927480

Cited by 33 publications

(8 citation statements)

References 21 publications

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“…However, we have observed higher renal Na,K-ATPase activities in ZDF fa/fa rats than those found in control rats. Thus, in the present study, the increase in oxidative stress was not associated with an impairment of Na,K-ATPase functionality as suggested previously [ 17 , 18 ]. The transport of Na + ions from the tubular cells is a prerequisite for the secondary active transport mechanisms involved in the reabsorption of multiple substances from the tubular fluid, including glucose.…”

Section: Discussionsupporting

confidence: 89%

“…Proximal tubular Na,K-ATPase enzyme activity was shown to be sensitive to oxidative modification [ 17 ]. It was suggested that the most significant consequence of oxidative injury is impaired Na,K-ATPase activity as well as the inability of Na,K-ATPase molecules to form oligomers and, in this way, interact with each other [ 18 ]. Taking this into consideration, we also aimed to monitor selected parameters reflecting the oxidative stress status in the renal tissue of all experimental animals.…”

Section: Introductionmentioning

confidence: 99%

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Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

Vrbjar

Jasenovec

Kollárová

et al. 2022

Biology

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For a better insight into relations between type 2 diabetes mellitus (T2DM) and Na,K-ATPase properties in kidneys, we aimed to characterize two subgroups of ZDF obese (fa/fa) rats, with more and less developed T2DM, and compare them with two controls: lean (fa/+) and Wistar. Na,K-ATPase enzyme kinetics were estimated by measuring the ATP hydrolysis in the range of NaCl and ATP levels. As Na,K-ATPase is sensitive to oxidative stress, we evaluated selected oxidative stress parameters in kidney homogenates. Our results suggest that thiol–disulfide redox balance in the renal medulla and Na,K-ATPase properties in the renal cortex differ between both controls, while observed measurements in lean (fa/+) rats showed deviation towards the values observed in ZDF (fa/fa) rats. In comparison with both controls, Na,K-ATPase enzyme activity was higher in the renal cortex of ZDF rats independent of diabetes severity. This might be a consequence of increased glucose load in tubular fluid. The increase in lipid peroxidation observed in the renal cortex of ZDF rats was not associated with Na,K-ATPase activity impairment. Regarding the differences between subgroups of ZDF animals, well-developed T2DM (glycemia higher than 10 mmol/L) was associated with a higher ability of Na,K-ATPase to utilize the ATP energy substrate.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

Vrbjar

Jasenovec

Kollárová

et al. 2022

Biology

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“…3,4 Na/K-ATPase is the target for oxidation and highly susceptible to oxidative damage directly. 14 In addition, the oxidation of Na/K-ATPase directly leads to excessive cation leak and a rapid increment of extracellular potassium ion (K + ) concentration. In return, the K + efflux from the cell activates pyrin domain-containing 3 (NLRP3) inflammasome, which induces ROS and exaggerates oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

“…Na/K-ATPase is a transmembrane enzyme for electrogenic ion transportation, responsible for high K + and low Na + concentration in the cytoplasm. Because it is a cellular oxidative stress target, Na/K-ATPase activity is readily inhibited by the excessive ROS, 14,15 and Na/K-ATPase deficiency induces increase in K + efflux and delay in rectifier K + channels, resulting in deteriorated K + homeostasis and high K + concentration in extracellular fluids. 16 On the contrary, Na/ K-ATPase is involved in signaling during oxidative stress to alter cellular mechanisms and plays a key role in maintaining K + homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Biomimicking Dual-Responsive Extracellular Matrix Restoring Extracellular Balance through the Na/K-ATPase Pathway

Luan

Wang

Xiang

et al. 2019

ACS Appl. Mater. Interfaces

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Biomedical implant mimicking the physiological extracellular matrix (ECM) is a new strategy to modulate the cell microenvironment to improve implant integrity and longevity. However, the biomimicking ECM suffers from low sensitivity to pathological change and low efficiency to restore the physiological state in vivo. To overcome these problems, reactive oxygen species (ROS) and K+ dual-responsive micro-/nanofibers that encapsulate ascorbic acid-2-glucoside (AA-2G) are fabricated on an elastomer substrate with electrospinning to mimic the ECM. The strategy is based on the fact that ROS and K+ dual responsiveness enhance the sensitivity of the ECM to pathological changes and delivery of AA-2G from the ECM to cell membrane promotes reactivating Na/K-ATPase and shifting cellular diseased conditions to the normal state. We demonstrate that the ROS and K+-responsive tripolymer of poly(ethylene glycol)diacrylate, 1,2-ethanedithiol, and 4-nitrobenzo-18-crown-6-ether (PEGDA–EDT–BCAm) are synthesized successfully; the ECM composed of acylated poly(caprolactone)/PEGDA–EDT–BCAm/AA-2G micro-/nanofibers is prepared through reactive electrospinning; the ECM is sensitive to ROS and K+ concentration in the microenvironment to release AA-2G, which targets the membrane to remove the excessive ROS and reactivate Na/K-ATPase; as a result, the ECM reduces oxidative stress and restores the extracellular physiological state both in vitro and in vivo. This work provides basic principles to design an implant that can adjust the extracellular microenvironment while avoiding pathogenicity to improve implant integrity and longevity in vivo.

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“…Additionally, chrysin treatment attenuated 6-OHDA-induced decreases in the levels of Na + and K + -ATPase in the ST of mice. Na + and K + -ATPase play a central role in maintaining ionic gradients and neuronal excitability and are more susceptible to oxidative damage [159].…”

Section: Neuroprotective Roles Of Phytochemicalsmentioning

confidence: 99%

Natural Phytochemicals as Novel Therapeutic Strategies to Prevent and Treat Parkinson’s Disease: Current Knowledge and Future Perspectives

Balakrishnan

Azam

Cho

et al. 2021

Oxidative Medicine and Cellular Longevity

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Parkinson’s disease (PD) is the second-most common neurodegenerative chronic disease affecting both cognitive performance and motor functions in aged people. Yet despite the prevalence of this disease, the current therapeutic options for the management of PD can only alleviate motor symptoms. Research has explored novel substances for naturally derived antioxidant phytochemicals with potential therapeutic benefits for PD patients through their neuroprotective mechanism, targeting oxidative stress, neuroinflammation, abnormal protein accumulation, mitochondrial dysfunction, endoplasmic reticulum stress, neurotrophic factor deficit, and apoptosis. The aim of the present study is to perform a comprehensive evaluation of naturally derived antioxidant phytochemicals with neuroprotective or therapeutic activities in PD, focusing on their neuropharmacological mechanisms, including modulation of antioxidant and anti-inflammatory activity, growth factor induction, neurotransmitter activity, direct regulation of mitochondrial apoptotic machinery, prevention of protein aggregation via modulation of protein folding, modification of cell signaling pathways, enhanced systemic immunity, autophagy, and proteasome activity. In addition, we provide data showing the relationship between nuclear factor E2-related factor 2 (Nrf2) and PD is supported by studies demonstrating that antiparkinsonian phytochemicals can activate the Nrf2/antioxidant response element (ARE) signaling pathway and Nrf2-dependent protein expression, preventing cellular oxidative damage and PD. Furthermore, we explore several experimental models that evaluated the potential neuroprotective efficacy of antioxidant phytochemical derivatives for their inhibitory effects on oxidative stress and neuroinflammation in the brain. Finally, we highlight recent developments in the nanodelivery of antioxidant phytochemicals and its neuroprotective application against pathological conditions associated with oxidative stress. In conclusion, naturally derived antioxidant phytochemicals can be considered as future pharmaceutical drug candidates to potentially alleviate symptoms or slow the progression of PD. However, further well-designed clinical studies are required to evaluate the protective and therapeutic benefits of phytochemicals as promising drugs in the management of PD.

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Na/K-ATPase under Oxidative Stress: Molecular Mechanisms of Injury

Cited by 33 publications

References 21 publications

Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity—Comparison with Lean (fa/+) and Wistar Rats

Biomimicking Dual-Responsive Extracellular Matrix Restoring Extracellular Balance through the Na/K-ATPase Pathway

Natural Phytochemicals as Novel Therapeutic Strategies to Prevent and Treat Parkinson’s Disease: Current Knowledge and Future Perspectives

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