Mechanisms of Activation of LRRC8 Volume Regulated Anion Channels

Bertelli, Sara; Zuccolini, Paolo; Barbieri, Raffaella; Ferrera, Loretta; Picco, Cristiana; Gavazzo, Paola; Pusch, Michael

doi:10.33594/000000329

Cited by 29 publications

(19 citation statements)

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“…In our study, we found that açai berry restored autophagic flux at physiological levels. Interesting studies have shown that the altered expression of MAP-2 and β-tubulin leads to neuronal death; such results could be used in the future target for neuroprotective therapy targeting [ 111 , 112 , 113 , 114 ]. In our work, we found that açai berry stops the process of cell death and neurodegeneration and restores the microtubule network.…”

Section: Discussionmentioning

confidence: 99%

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways

Impellizzeri

D’Amico

Fusco

et al. 2022

Cells

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The second-most common cause of dementia is vascular dementia (VaD). The majority of VaD patients experience cognitive impairment, which is brought on by oxidative stress and changes in autophagic function, which ultimately result in neuronal impairment and death. In this study, we examine a novel method for reversing VaD-induced changes brought on by açai berry supplementation in a VaD mouse model. The purpose of this study was to examine the impact of açai berries on the molecular mechanisms underlying VaD in a mouse model of the disease that was created by repeated ischemia–reperfusion (IR) of the whole bilateral carotid artery. Here, we found that açai berry was able to reduce VaD-induced behavioral alteration, as well as hippocampal death, in CA1 and CA3 regions. These effects are probably due to the modulation of nuclear factor erythroid 2-related factor 2 (Nrf-2) and Beclin-1, suggesting a possible crosstalk between these molecular pathways. In conclusion, the protective effects of açai berry could be a good supplementation in the future for the management of vascular dementia.

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Section: Discussionmentioning

confidence: 99%

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways

Impellizzeri

D’Amico

Fusco

et al. 2022

Cells

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“…In physiological conditions, the production of reactive oxygen and nitrogen species generated during cellular metabolism in biological systems is balanced by the ability of the latter to defend through their sophisticated antioxidant machinery. Nevertheless, when oxidants are produced in excess, or when the antioxidant defenses that regulate them are ineffective, this balance can be perturbed, thus resulting in oxidative stress (OS) [ 4 , 7 , 8 , 9 , 10 ]. In these conditions, biomolecules can be altered through oxidation to an extent that exceeds repair capacity.…”

Section: Introductionmentioning

confidence: 99%

Açaì (Euterpe oleracea) Extract Protects Human Erythrocytes from Age-Related Oxidative Stress

Spinelli

Straface

Gambardella

et al. 2022

Cells

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Aging is a process characterised by a general decline in physiological functions. The high bioavailability of reactive oxygen species (ROS) plays an important role in the aging rate. Due to the close relationship between aging and oxidative stress (OS), functional foods rich in flavonoids are excellent candidates to counteract age-related changes. This study aimed to verify the protective role of Açaì extract in a d-Galactose (d-Gal)-induced model of aging in human erythrocytes. Markers of OS, including ROS production, thiobarbituric acid reactive substances (TBARS) levels, oxidation of protein sulfhydryl groups, as well as the anion exchange capability through Band 3 protein (B3p) and glycated haemoglobin (A1c) have been analysed in erythrocytes treated with d-Gal for 24 h, with or without pre-incubation for 1 h with 0.5–10 µg/mL Açaì extract. Our results show that the extract avoided the formation of acanthocytes and leptocytes observed after exposure to 50 and 100 mM d-Gal, respectively, prevented d-Gal-induced OS damage, and restored alterations in the distribution of B3p and CD47 proteins. Interestingly, d-Gal exposure was associated with an acceleration of the rate constant of SO42− uptake through B3p, as well as A1c formation. Both alterations have been attenuated by pre-treatment with the Açaì extract. These findings contribute to clarify the aging mechanisms in human erythrocytes and propose functional foods rich in flavonoids as natural antioxidants for the treatment and prevention of OS-related disease conditions.

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“…LRRC8A-E/SWELL1 proteins are essential components of the volume-regulated outwardly rectifying Cl – current (VRAC, VSOR, VSOAC, ICl swell , ICl vol ) elicited in most cells during cell swelling ( Qiu et al, 2014 ; Voss et al, 2014 ; Jentsch, 2016 ; Jentsch et al, 2016 ; Okada, 2020 ; Bertelli et al, 2021 ), and they are involved in a broad variety of cellular functions ( Chen et al, 2019 ). LRRC8A-E/SWELL1 also regulate the PI3K-Akt, Erk1/2, mTOR signaling cascade ( Kumar et al, 2020 ; Alghanem et al, 2021 ).…”

Section: Water Ions and Their Channels And Transporters In Pinocytosismentioning

confidence: 99%

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

Ritter

Bresgen

Kerschbaum

2021

Front. Cell Dev. Biol.

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The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell’s surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nor fuse with lysosomes but with each other to form giant vacuoles, which finally cause rupture of the plasma membrane (PM). Understanding methuosis longs for the understanding of the ionic mechanisms of cell volume regulation (CVR) and vesicular volume regulation (VVR). In nascent macropinosomes, ion channels and transporters are derived from the PM. Along trafficking from the PM to the perinuclear area, the equipment of channels and transporters of the vesicle membrane changes by retrieval, addition, and recycling from and back to the PM, causing profound changes in vesicular ion concentrations, acidification, and—most importantly—shrinkage of the macropinosome, which is indispensable for its proper targeting and cargo processing. In this review, we discuss ion and water transport mechanisms with respect to CVR and VVR and with special emphasis on pinocytosis and methuosis. We describe various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement.

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Mechanisms of Activation of LRRC8 Volume Regulated Anion Channels

Cited by 29 publications

References 0 publications

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways

Açaì (Euterpe oleracea) Extract Protects Human Erythrocytes from Age-Related Oxidative Stress

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

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