Ouabain-Na+/K+-ATPase Signaling Regulates Retinal Neuroinflammation and ROS Production Preventing Neuronal Death by an Autophagy-Dependent Mechanism Following Optic Nerve Axotomy In Vitro

Mázala-de-Oliveira, Thalita; Figueiredo, Camila Saggioro de; Corrêa, Gustavo de Rezende; Silva, Mayra Santos da; Miranda, Renan Lyra; Azevedo, Mariana Almeida de; Cossenza, Marcelo; Santos, Aline Araújo dos; Giestal-de-Araujo, Elizabeth

doi:10.1007/s11064-021-03481-0

Cited by 12 publications

(9 citation statements)

References 100 publications

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“…Likewise, the concept of NKA’s role as a receptor triggering a range of signaling pathways that subsequently affect cellular processes has expanded and diversified with new findings. Thus, it is now known that such activity occurs across various cell types beyond heart muscle and epithelia, including neurons [ 265 ] and sperm cells [ 266 ]. Furthermore, there is a growing acknowledgment of pathological processes involving NKA’s engagement as a receptor, where its interaction with GCs can either instigate or alleviate these conditions.…”

Section: Discussion and Perspectivementioning

confidence: 99%

Na+/K+-ATPase: More than an Electrogenic Pump

Contreras,

Torres-Carrillo,

Flores-Maldonado

et al. 2024

IJMS

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The sodium pump, or Na+/K+-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na+) and potassium (K+) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA’s role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell–cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells.

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Section: Discussion and Perspectivementioning

confidence: 99%

Na+/K+-ATPase: More than an Electrogenic Pump

Contreras,

Torres-Carrillo,

Flores-Maldonado

et al. 2024

IJMS

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“…Additionally, the significant inhibition of Na + –K + ATPase may be caused by a series of responses resulting from PAT exposure. First, PAT stress induces excessive intracellular ROS production, leading to the dysregulation of antioxidant systems, such as SOD enzyme activity, as well as an increase in malondialdehyde content, which can alter cell membrane permeability, integrity, and depolarization, and ultimately cause a decrease in ATPase activity [ 29 , 30 ]. Similar to the antioxidant system response, the inhibition of LDH and ATPase also diminished with increasing PAT exposure time.…”

Section: Discussionmentioning

confidence: 99%

Insights into the Metabolic Response of Lactiplantibacillus plantarum CCFM1287 upon Patulin Exposure

Wei

Zhang

Gao

et al. 2022

IJMS

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Patulin (PAT) is a common mycotoxin in the food industry, and is found in apple products in particular. Consumption of food or feed contaminated with PAT can cause acute or chronic toxicity in humans and animals. Lactiplantibacillus plantarum CCFM1287 is a probiotic strain that effectively degrades PAT in PBS and food systems. In this study, it was found that the concentration of PAT (50 mg/L) in MRS medium decreased by 85.09% during the first stages of CCFM1287 growth, and this change was consistent with the first-order degradation kinetic model. Meanwhile, the regulation of oxidative stress by L. plantarum CCFM1287 in response to PAT exposure and metabolic changes that occur during PAT degradation were investigated. The degree of intracellular damage was attenuated after 16 h of exposure compared to 8 h. Meanwhile, metabolomic data showed that 30 and 29 significantly different metabolites were screened intracellularly in the strain after 8 h and 16 h of PAT stress at 50 mg/L, respectively. The results of pathway enrichment analysis suggested that the purine metabolic pathway was significantly enriched at both 8 h and 16 h. However, as is consistent with the performance of the antioxidant system, the changes in Lactiplantibacillus diminished with increasing time of PAT exposure. Therefore, this study helps to further explain the mechanism of PAT degradation by L. plantarum CCFM1287.

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“…However, studies have indicated that ouabain promotes RGC survival after optic nerve axotomy through NKA-mediated activation of Src kinase and subsequent transactivation of the epidermal growth factor receptor, as well as the activation of the PKC delta and c-Jun N-terminal kinase signaling pathways [440,452]. In retinal cells, recent evidence indicates that ouabain prevents RGC death through stimulating autophagy [453]. In addition, ouabain also decreases oxidative stress, modulates microglial reactivity, and regulates the expression of cytokines such as brain-derived neurotrophic factor, TNF-α, and interleukin 1-β [453,454], which are critical for neuronal survival and glial functions.…”

Section: Neuroprotectionmentioning

confidence: 99%

“…In retinal cells, recent evidence indicates that ouabain prevents RGC death through stimulating autophagy [453]. In addition, ouabain also decreases oxidative stress, modulates microglial reactivity, and regulates the expression of cytokines such as brain-derived neurotrophic factor, TNF-α, and interleukin 1-β [453,454], which are critical for neuronal survival and glial functions. Thus, future studies on the physiological functions of NKA-mediated neuron-glia signaling, as well as in retinal disease models, may contribute to the development of new therapeutic strategies against retinal degeneration.…”

Section: Neuroprotectionmentioning

confidence: 99%

The Healthy and Diseased Retina Seen through Neuron–Glia Interactions

Tempone,

Borges-Martins,

César

et al. 2024

IJMS

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The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

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Ouabain-Na+/K+-ATPase Signaling Regulates Retinal Neuroinflammation and ROS Production Preventing Neuronal Death by an Autophagy-Dependent Mechanism Following Optic Nerve Axotomy In Vitro

Cited by 12 publications

References 100 publications

Na+/K+-ATPase: More than an Electrogenic Pump

Na+/K+-ATPase: More than an Electrogenic Pump

Insights into the Metabolic Response of Lactiplantibacillus plantarum CCFM1287 upon Patulin Exposure

The Healthy and Diseased Retina Seen through Neuron–Glia Interactions

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