Functional interactions between oxidative stress, membrane Na+ permeability, and cell volume in rat hepatoma cells

Schlenker, Thorsten; Feranchak, Andrew P.; Schwake, Lukas; Stremmel, Wolfgang; Roman, Richard M.; Fitz, John

doi:10.1016/s0016-5085(00)70222-8

Cited by 28 publications

(39 citation statements)

References 27 publications

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“…The molecular identity of the channels involved has not been defined, but they appear to be equally permeable to Na ϩ and K ϩ ions and show an ohmic current-voltage relationship, suggesting that they may be members of the nonselective cation family. 17 In contrast, increases in membrane K ϩ and Cl Ϫ permeability provide a powerful counterpoint, and represent the major driving force for water movement out of the cell. 18 While the molecular iden-tity of the K ϩ channels is not known, a portion of the volumesensitive Cl Ϫ conductance appears to be mediated by ClC-2 chloride channels that have been cloned and identified in liver cells at the level of cDNA, mRNA, and functional protein.…”

Section: Role Of Ion Channels In Liver Cell Volume Regulation: Primarmentioning

confidence: 99%

Liver Cell Volume Regulation: Size Matters

2001

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Liver cells are located in a critical anatomic site, with dual perfusion by both the portal and systemic circulations. Consequently, they are subject to unusually large changes in the concentrations of solutes such as amino acids, bile acids, and glucose between the fed and fasted states. Because these solutes are concentrated intracellularly, and osmolar gradients as low as ϳ1 mosm⅐L Ϫ1 are sufficient to induce transmembrane water movement, liver cell volume can increase by 5% to 10% in response to increased solute uptake. 1 These primary changes in volume are followed after a delay by compensatory increases in membrane ion permeability of 20-fold or more (Fig. 1), and the resulting shift toward net solute efflux represents a critical adaptive response that favors passive water movement and restoration of cell volume toward basal values. 2 Volume recovery is usually incomplete, however, and there is emerging evidence that the small residual differences from baseline, either positive or negative, act as a signal that directly influences a broad range of processes including kinase activation, gene expression, and membrane transport. 3 In this brief review, the emerging evidence supporting the presence of functional interactions between solute transport, intracellular metabolism, and cell volume is explored. Emphasis is placed on the role of ion channels and membrane transport in cell volume regulation, and the evolution of evidence that cell volume as a critical determinant of liver cell and organ function is summarized as well.

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Section: Role Of Ion Channels In Liver Cell Volume Regulation: Primarmentioning

confidence: 99%

Liver Cell Volume Regulation: Size Matters

2001

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“…These cells express insulin receptors, ion channels, and signaling pathways similar to those found in primary rat hepatocytes (5,6,(21)(22)(23). Decreases in cell volume caused by exposure to hypertonic buffer or oxidative stress are followed by Na ϩ influx through opening of NSC channels in the plasma membrane (5,6). Cells were passaged at weekly intervals and maintained at 37°C, 5% CO 2 in HCO 3 Ϫ -containing minimal essential media (Invitrogen) supplemented with heat-inactivated fetal bovine serum (10%) and L-glutamine (2 mM).…”

Section: Methodsmentioning

confidence: 76%

“…The standard intracellular (pipette) solution contained (in mM): 130 KCl, 10 NaCl, 2 MgCl 2 , 10 HEPES/KOH, 0.5 CaCl 2 , and 1 EGTA (pH 7.3), corresponding to a free [Ca 2ϩ ] of ϳ100 nM (6). With these solutions, inward currents at a test potential of Ϫ80 mV are carried by influx of Na ϩ ions (5,25). The ionic selectivity of currents was confirmed by partial substitution of extracellular Na ϩ with equimolar concentrations of K ϩ or Tris ϩ as indicated.…”

Section: Methodsmentioning

confidence: 89%

“…In addition, failure to regulate cell volume has been implicated in liver cell injury associated with alcohol, ischemia/ reperfusion, and organ preservation (3,4). Consequently, the definition of the sensing and regulatory mechanisms involved has broad implications for the modulation of liver cell and organ function as well as cellular response to injury (5).…”

Section: In Liver Cells the Influx Of Namentioning

confidence: 99%

“…Under basal conditions, membrane Na ϩ permeability is low because of tonic inhibition of channels by p38 mitogen-activated protein (MAP) 1 kinase, a human homologue of the Saccharomyces cerevisiae HOG-1 gene product essential for cellular osmoregulation (6). Decreases in cell volume stimulated by oxidative stress and/or hypertonic exposure initiate an adaptive response that leads within minutes to Na ϩ influx through opening of nonselective cation (NSC) channels (5,7). The resulting movement of water into the cell contributes to the restoration of volume toward basal values, a general process referred to as regulatory volume increase (RVI).…”

Section: In Liver Cells the Influx Of Namentioning

confidence: 99%

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Volume-sensitive Tyrosine Kinases Regulate Liver Cell Volume through Effects on Vesicular Trafficking and Membrane Na+ Permeability

Feranchak

Kilic

Wojtaszek

et al. 2003

Journal of Biological Chemistry

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In liver cells, the influx of Na؉ mediated by nonselective cation (NSC) channels in the plasma membrane contributes importantly to regulation of cell volume. Under basal conditions, channels are closed; but both physiologic (e.g. insulin) and pathologic (e.g. oxidative stress) stimuli that are known to stimulate tyrosine kinases are associated with large increases in membrane Na ؉ permeability to ϳ80 pA/pF or more. Consequently, the purpose of these studies was to evaluate whether volumesensitive tyrosine kinases mediate cell volume increases through effects on the activity or distribution of NSC channel proteins. In HTC hepatoma cells, decreases in cell volume evoked by hypertonic exposure increased total cellular tyrosine kinase activity ϳ20-fold. Moreover, hypertonic exposure (320 -400 mosM) was followed after a delay by NSC channel activation and partial recovery of cell volume toward basal values (regulatory volume increase (RVI)). The tyrosine kinase inhibitors genistein and erbstatin prevented both NSC channel activation and RVI. Similarly, hypertonic exposure resulted in an increase in p60 c-src activity, and intracellular dialysis with recombinant p60 c-src led to activation of NSC currents in the absence of an osmolar gradient. Utilizing FM1-43 fluorescence, exposure to hypertonic media caused a rapid increase in the rate of exocytosis of ϳ40% (p < 0.01), and genistein inhibited both exocytosis and channel activation. These findings indicate that volume-sensitive increases in p60 c-src and/or related tyrosine kinases play a key role in the regulation of membrane Na ؉ permeability, suggesting that increases in the NSC conductance may be mediated in part through rapid recruitment of a distinct pool of channelcontaining vesicles.

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Characterization of ionotrophic purinergic receptors in hepatocytes

et al. 2008

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Ionotrophic purinergic (P2X) receptors function as receptor-gated cation channels, where agonist binding leads to opening of a nonselective cation pore permeable to both Na ؉ and Ca 2؉ . Based on evidence that extracellular adenosine 5-triphosphate (ATP) stimulates glucose release from liver, these studies evaluate whether P2X receptors are expressed by hepatocytes and contribute to ATP-dependent calcium signaling and glucose release. Studies were performed in isolated hepatocytes from rats and mice and hepatoma cells from humans and rats. Transcripts and protein for both P2X4 and P2X7 were detectable, and immunohistochemistry of intact liver revealed P2X4 in the basolateral and canalicular domains. H epatocytes exhibit regulated release of adenosine 5Ј-triphosphate (ATP) into the extracellular space. 1 Once outside the cell, these nucleotides function as potent autocrine/paracrine signaling molecules that modulate liver function through activation of purinergic receptors in the plasma membrane. Initially discovered in neurons, purinergic receptors are implicated in the control of a spectrum of essential physiologic mechanisms ranging from vascular tone to programmed cell death. In the liver, nanomolar concentrations of ATP, or its breakdown products, activate Cl Ϫ channels, decrease cell volume, and stimulate bile flow. 2,3 Moreover, exposure of perfused isolated livers to ATP stimulates a large release of glucose. 4 Collectively, these coordinated pathways of ATP release, receptor binding, and degradation constitute a versatile mechanism for paracrine regulation of liver function.These diverse effects of ATP are not readily explained by a single receptor type. Previous studies indicate that hepatocytes express several subtypes of G-protein coupled P2Y receptors, including P2Y1, P2Y2, P2Y4, and P2Y6. Selective stimulation of P2Y2 receptors activates plasma membrane chloride channels and stimulates ductular bile secretion. 5 P2Y receptors also appear to play a role in the activation of glycogen phosphorylase, the rate-controlling enzyme in hepatic glycogenolysis, 6 and regulate multiple signaling pathways with changes in cellular [Ca 2ϩ ], eicosanoid production, and cyclic adenosine monophosphate

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Functional interactions between oxidative stress, membrane Na+ permeability, and cell volume in rat hepatoma cells

Cited by 28 publications

References 27 publications

Liver Cell Volume Regulation: Size Matters

Liver Cell Volume Regulation: Size Matters

Volume-sensitive Tyrosine Kinases Regulate Liver Cell Volume through Effects on Vesicular Trafficking and Membrane Na+ Permeability

Characterization of ionotrophic purinergic receptors in hepatocytes

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