Regulation of cytosol–nucleus pH gradients by K+/H+ exchange mechanism in the nuclear envelope of neonatal rat astrocytes

Masuda, Akira; Oyamada, Masahito; Nagaoka, Takanori; Tateishi, Narito; Takamatsu, Tetsuro

doi:10.1016/s0006-8993(98)00737-9

Cited by 44 publications

(32 citation statements)

References 33 publications

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“…Nuclear membranes and nucleoplasm contain a number of signaling factors possibly involved in both PAF and LPA 1 receptor signal transduction pathways. For instance, nuclear localization has been identified for G proteins (G i/o , G sα ) (Takei et al 1994;Saffitz et al 1994;Balboa and Insel 1995); calcium channels and pumps (inositol tri-and tetraphosphat [IP 3 , IP 4 ] and ryanodine receptors, Ca 2+ -ATPase pump, Na + /Ca 2+ exchanger) (Malviya et al 1990;Gerasimenko et al 1996;Xie et al 2002); ion channels (K + , Na + , Cl − , Ca 2+ , Zn + , K + /H + exchanger, Na + /K + -pump) (Mazzanti et al 1990;Maruyama et al 1995;Szweczyk 1998;Masuda et al 1998;Garner 2002); phospholipases A 2 , D, and C (Divecha and Irvin, 1995;D'Santos et al 1998;Cocco et al 1999); adenylyl cyclase (Yamamoto et al 1998); protein kinase C (Buchner 1995); MAPK (Erk1, Erk2, Erk3) (Cheng et al 1996;Kim and Kahn 1997;Thomson et al 1999); and IκB and NF-κB (Sachdev et al 1998;Karin and Ben-Nariah 2000). The autonomous nature of the nuclear signaling network brings a new dimension to cellular signaling, somewhat independent from plasma membrane/cytosolic events.…”

Section: Nuclear Signaling Pathwaysmentioning

confidence: 99%

Intracellular Signaling of Lipid Mediators via Cognate Nuclear G Protein–Coupled Receptors

et al. 2005

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Platelet-activating factor (PAF) and lysophosphatidic acid (LPA) are ubiquitous lipid mediators that play important roles in inflammation, cardiovascular homeostasis, and immunity and are also known to modulate gene expression of specific proinflammatory genes. The mechanism of action of these phospholipids is thought to be primarily dependent on their specific plasma membrane receptors belonging to the superfamily of G protein-coupled receptors (GPCRs). However, increasing evidence suggests the existence of a functional intracellular GPCR population. It has been suggested that immediate effects are mediated by cell surface receptors, whereas long-term responses are mediated by intracellular receptors. PAF and LPA(1) receptors localize at the cell nucleus of cerebral microvascular endothelial cells of newborn pig, rat hepatocytes, and cells overexpressing each receptor, and stimulation of isolated nuclei reveal biological functions, including transcriptional regulation of major genes, namely cylooxygenase-2 and inducible nitric oxide synthase. This mini review focuses on the nuclear localization and signaling of GPCRs, recognizing PAF and LPA phospholipids as ligands. Theories on how nuclear PAF and LPA1 receptors activate gene transcription and nuclear localization pathways are discussed. Intracrine signaling for lipid mediators uncover novel pathways to elicit their effects; moreover, intracellular GPCRs constitute a distinctive mode of action for gene regulation.

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Section: Nuclear Signaling Pathwaysmentioning

confidence: 99%

Intracellular Signaling of Lipid Mediators via Cognate Nuclear G Protein–Coupled Receptors

et al. 2005

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“…Given that the photometric fluorescence system consisted of two fibre optics which could move in an analog fashion over the image, correction for both of these artefacts would have been very difficult. The extent to which such calibration problems apply to others who have reported steady-state pH gradients [see Discussion in 14,15,29] is unclear. Indeed, the apparent pH i microdomains published by Ro and Carson [16] are almost certainly the result of imaging artefacts.…”

Section: Calibration Artefactsmentioning

confidence: 99%

“…In this paper, we have tested whether or not neuronal pH i is uniform under resting conditions [13][14][15][16] and investigated experimentally the effect of neuronal morphology and mobile pH buffers on the time course of the local pH i signals [12]. We have used snail neurons in this study as they are experimentally tractable and have wellcharacterized pH-regulating mechanisms [3,6,17], including voltage-gated proton channels that allow very rapid and non-uniform changes in pH i [4,18].…”

Section: Introductionmentioning

confidence: 99%

The effect of neuronal morphology and membrane-permeant weak acid and base on the dissipation of depolarization-induced pH gradients in snail neurons

Pantazis

Keegan

Postma

et al. 2005

Pflugers Arch - Eur J Physiol

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Neuronal depolarization causes larger intracellular pH (pH(i)) shifts in axonal and dendritic regions than in the cell body. In this paper, we present evidence relating the time for collapse of these gradients to neuronal morphology. We have used ratiometric pH(i) measurements using 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) in whole-cell patch-clamped snail neurons to study the collapse of longitudinal pH gradients. Using depolarization to open voltage-gated proton channels, we produced alkaline pH(i) microdomains. In the absence of added mobile buffers, facilitated H(+) diffusion down the length of the axon plays a critical role in determining pH(i) microdomain lifetime, with axons of approximately 100 microm allowing pH differences to be maintained for >60 s. An application of mobile, membrane-permeant pH buffers accelerated the collapse of the alkaline-pH gradients but, even at 30 mM, was unable to abolish them. Modeling of the pH(i) dynamics showed that both the relatively weak effect of the weak acid/base on the peak size of the pH gradient and the accelerated collapse of the pH gradient could be due to the time taken for equilibration of the weak acid and base across the cell. We propose that appropriate weak acid/base mixes may provide a simple method for studying the role of local pH(i) signals without perturbing steady-state pH(i). Furthermore, an extrapolation of our in vitro data to longer and thinner neuronal structures found in the mammalian nervous system suggests that dendritic and axonal pH(i) are likely to be dominated by local pH(i)-regulating mechanisms rather than simply following the soma pH(i).

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“…The nucleus has the ability to regulate its own pH which is typically slightly higher than that of the cytoplasm 25 and under acidic conditions, the nuclear pH may not drop as much as the cytoplasmic pH. 26 In our work presented here, changes in nuclear and cytoplasmic scattering were measured in intact cells and the results demonstrate that the change in nuclear light scattering when acetic acid is present is greater than that of the cytoplasm.…”

Section: Discussionmentioning

confidence: 59%

Effects of acetic acid on light scattering from cells

Marina

2012

J. Biomed. Opt

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Abstract. Acetic acid has been used for decades as an aid for the detection of precancerous cervical lesions, and the use of acetic acid is being investigated in several other tissues. Nonetheless, the mechanism of acetowhitening is unclear. This work tests some of the hypotheses in the literature and measures changes in light scattering specific to the nucleus and the cytoplasm. Wide angle side scattering from both the nucleus and the cytoplasm increases with acetic application to tumorigenic cells, with the increase in nuclear scattering being greater. In one cell line, the changes in nuclear scattering are likely due to an increase in number or scattering efficiency of scattering centers smaller than the wavelength of excitation light. There are likely several cellular changes that cause acetowhitening and the cellular changes may differ with cell type. These results should lead to a better understanding of acetowhitening and potentially the development of adjunct techniques to improve the utility of acetic acid application. For the well-studied case of cervical tissue, acetowhitening has been shown to be sensitive, but not specific for oncogenic changes needing treatment.

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Regulation of cytosol–nucleus pH gradients by K+/H+ exchange mechanism in the nuclear envelope of neonatal rat astrocytes

Cited by 44 publications

References 33 publications

Intracellular Signaling of Lipid Mediators via Cognate Nuclear G Protein–Coupled Receptors

Intracellular Signaling of Lipid Mediators via Cognate Nuclear G Protein–Coupled Receptors

The effect of neuronal morphology and membrane-permeant weak acid and base on the dissipation of depolarization-induced pH gradients in snail neurons

Effects of acetic acid on light scattering from cells

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