Arachidonic Acid Activates K+-Cl--cotransport in HepG2 Human Hepatoblastoma Cells

Lee, Yong Soo

doi:10.4196/kjpp.2009.13.5.401

Cited by 6 publications

(2 citation statements)

References 58 publications

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“…It was shown that AA markedly increases AP-1 binding to DNA in HepG2 cells and this effect was potentiated by oxidative stress (Bai and Cederbaum 2000 ). Exogenous AA has also been shown to alter p38 mitogen-activated protein kinase pathway in neural cells (Wood et al 2000 ) and to induce K(+) efflux via K + -Cl − -cotransport in HepG2 cells (Lee 2009 ). Alterations in intracellular ion balance and kinase signaling may be important to cell growth and survival; however, at higher AA concentrations, such effects appear to be less relevant due to critical role of oxidative stress, cell membrane damage, and rapid necrotic cell death.…”

Section: Discussionmentioning

confidence: 99%

Histone acetylation and arachidonic acid cytotoxicity in HepG2 cells overexpressing CYP2E1

Hołownia

Mróz

Wielgat

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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The aim of this work was to assess the role of ethanol-derived acetate and acetate-mediated histone acetylation in arachidonic acid-induced stress in HepG2 cells and cells overexpressing CYP2E1. Cells were grown for 7 days with 1 mM sodium acetate or 100 mM ethanol; their acetylated histone proteins and histone deacetylase 2 expression was quantified using Western blot. Ethanol- or acetate-pretreated cells were also treated for 24 h with 60 μM arachidonic acid to induce oxidative stress. Cytotoxicity was estimated by lactate dehydrogenase release, 3-[4,5-dimethylthiazolyl-2] 2,5-diphenyltetrazolium bromide test, and by DNA damage, while oxidative stress was quantified using dichlorofluorescein diacetate. Cells grown with ethanol or acetate had increased acetylated histone H3 levels in both cell types and elevated acetylated histone H4 levels in cells overexpressing CYP2E1 but not in naïve cells. In cells overexpressing CYP2E1 grown with ethanol, expression of histone deacetylase 2 was reduced by about 40 %. Arachidonic acid altered cell proliferation and was cytotoxic mostly to cells engineered to overexpress CYP2E1 but both effects were significantly lower in cells pretreated with ethanol or acetate. Cytotoxicity was also significantly decreased by 4-methylpyrazole—a CYP2E1 inhibitor and by trichostatin—an inhibitor of histone deacetylases. In cells pretreated with acetate or ethanol, the oxidative stress induced by arachidonic acid was also significantly lower. Our data indicate that histone hyperacetylation may in some extent protect the cells against oxidative stress. It is possible that acetate may act as an antioxidant at histone level. This mechanism may be relevant to alcohol-induced liver injury.

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Section: Discussionmentioning

confidence: 99%

Histone acetylation and arachidonic acid cytotoxicity in HepG2 cells overexpressing CYP2E1

Hołownia

Mróz

Wielgat

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Figures 8A and B visualize representative cells with blebbing DCPIB (20 µM). Since DIOA blocks Cl - -channels [3,22] as well as KCC [3,22,23,24,25,26], these may cause an imbalance in Cl - or intracellular pH homeostasis, because Cl - -channels and transporters are also permeable to HCO 3 - [9,27]. …”

Section: Resultsmentioning

confidence: 99%

Chloride Channel Blockers Suppress Formation of Engulfment Pseudopodia in Microglial Cells

Harl

Schmölzer

Jakab

et al. 2013

Cell Physiol Biochem

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Background/Aims: Phagocytosis depends on the formation of engulfment pseudopodia surrounding the target. We tested in microglia, monocyte-derived cells in the brain, whether a swelling-activated Cl^--current (I_Cl,_swell), required for global cell volume (CV) regulation, also contributes to local expansion and retraction of engulfment pseudopodia. Methods: We used scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to visualize and quantify the uptake of polystyrene microbeads (MBs) by microglial cells. Flow cytometry was used for cell volume measurments and I_Cl,_swell was measured by whole-cell patch clamp. Results: We found that exposure of microglial BV-2 cells to MBs in Cl^--free extracellular solution attenuated MB uptake and that the Cl^--channel blockers DIOA, flufenamic acid, NPPB and DCPIB suppressed the uptake of MBs in BV-2 cells and in primary microglial cells. Microglial cells exposed to MBs in the presence of Cl^- channel blockers failed to extend engulfment pseudopodia. We observed that cells containing at least three MBs revealed an about twofold increase in current density of I_{Cl, swell} compared to cells without MB. Osmotic challenges to stimulate global CV regulation before exposure to MBs modulated phagocytosis. Pre-conditioning of cells in hypo- or hypertonic medium for 12-16 hours caused a decrease in MB uptake. Conclusion: These findings indicate that I_Cl,_swell contributes to formation of engulfment pseudopodia and participates in engulfment and particle uptake in microglial cells.

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Potentiation of Regulatory Volume Decrease by a P2-Like Receptor and Arachidonic Acid in American Alligator Erythrocytes

et al. 2011

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This study examined the role of a P2 receptor and arachidonic acid (AA) in regulatory volume decrease (RVD) by American alligator red blood cells (RBCs). Osmotic fragility was determined optically, mean cell volume was measured by electronic sizing, and changes in intracellular Ca(2+) concentration were visualized using fluorescence microscopy. Gadolinium (50 μM), hexokinase (2.5 U/ml), and suramin (100 μM) increased osmotic fragility, blocked volume recovery after hypotonic shock, and prevented a rise in intracellular Ca(2+) that normally occurs during cell swelling. The P2X antagonists PPADS (50 μM) and TNP-ATP (10 μM) also increased fragility and inhibited volume recovery. In contrast, ATPγS (10 μM), α,β-methylene-ATP (50 μM) and Bz-ATP (50 μM) had the opposite effect, whereas 2-methylthio-ATP (50 μM) and UTP (10 μM) had no effect. In addition, the phospholipase A(2) (PLA(2)) inhibitors ONO-RS-082 (10 μM), chlorpromazine (10 μM), and isotetrandrine (10 μM) increased osmotic fragility and blocked volume recovery, whereas AA (10 μM) and its nonhydrolyzable analog eicosatetraynoic acid (ETYA, 10 μM) had the reverse effect. Further, AA (10 μM), but not ATPγS (10 μM), prevented the inhibitory effect of a low Ca(2+)-EGTA Ringer on RVD, whereas both AA (10 μM) and ATPγS (10 μM) caused cell shrinkage under isosmotic conditions. In conclusion, our results are consistent with the presence of a P2-like receptor whose activation stimulated RVD. In addition, AA also was important for volume recovery.

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Arachidonic Acid Activates K+-Cl--cotransport in HepG2 Human Hepatoblastoma Cells

Cited by 6 publications

References 58 publications

Histone acetylation and arachidonic acid cytotoxicity in HepG2 cells overexpressing CYP2E1

Histone acetylation and arachidonic acid cytotoxicity in HepG2 cells overexpressing CYP2E1

Chloride Channel Blockers Suppress Formation of Engulfment Pseudopodia in Microglial Cells

Potentiation of Regulatory Volume Decrease by a P2-Like Receptor and Arachidonic Acid in American Alligator Erythrocytes

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