The Vacuolar-Type<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mtext>H</mml:mtext><mml:mtext>+</mml:mtext></mml:msup></mml:mrow></mml:math>-ATPase in Ovine Rumen Epithelium is Regulated by Metabolic Signals

Kuzinski, Judith; Žitňan, R.; Warnke-Gurgel, Christina; Schweigel, Monika

doi:10.1155/2010/525034

Cited by 5 publications

(8 citation statements)

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“…Thus, in yeast, it was early shown that vacuolar V-ATPases rapidly disassemble upon glucose deprivation and they reassemble when the sugar is added back to the growth medium [37]. This same behaviour has been observed in renal epithelial cells [38,39] and, probably, it plays a role in other tissues, as suggested by results on ovine rumen [40]. The first indication of a regulatory link between carbohydrate metabolism and reversible assembly of the H + -pump came from osteoclasts and kidney cells, where aldolase was identified as an interacting partner with subunit E that influenced the assembly of the holoenzyme [41].…”

Section: Structure Of V-atpasesmentioning

confidence: 58%

Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer

Hernández

Serrano-Bueno²,

Perez-Castiñeira³

et al. 2012

CPD

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Cancer cells show a metabolic shift that makes them overproduce protons; this has the potential to disturb the cellular acid-base homeostasis. However, these cells show cytoplasmic alkalinisation, increased acid extrusion and endosome-dependent drug resistance. Vacuolar type ATPases (V-ATPases), together with other transporters, are responsible to a great extent for these symptoms. These multi-subunit proton pumps are involved in the control of cytosolic pH and the generation of proton gradients (positive inside) across endocellular membrane systems like Golgi, endosomes or lysosomes. In addition, in tumours, they have been shown to play an important role in the acidification of the intercellular medium. This importance makes them an attractive target to control tumour cell proliferation. In the present review we present the major characteristics of this kind of proton pumps and we provide some recent insights on their in vivo regulation. Also, we review some of the consequences that V-ATPase inhibition carries for the tumour cell, such as cell cycle arrest or cell death, and provide a brief summary of the studies related to cancer made recently with commercially available inhibitors. In the light of recent knowledge on the regulation of this proton pump, some new approaches to impair V-ATPase function are also suggested.

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Section: Structure Of V-atpasesmentioning

confidence: 58%

Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer

Hernández

Serrano-Bueno²,

Perez-Castiñeira³

et al. 2012

CPD

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“…Moreover, an antiapoptotic function for the B subunit of vH ϩ -ATPase has been proposed by various groups (16,29). In our previous study (28), the expression of the regulative vH ϩ -ATPase B subunit protein was drastically reduced or absent in rumen epithelium protein extracts from sheep with prolonged energy deficiency. Here, when compared with h-fed sheep, we found a higher total number of vH ϩ -ATPase B subunit expressing cells and, in F3-5 REC populations, also a higher amount of vH ϩ -ATPase B subunit protein, which could mean a lower rate of apoptosis.…”

Section: Discussionmentioning

confidence: 74%

“…As in our previous experiments (28), the effect of substrate and/or energy deficiency has been investigated, the aim of the present study has been to explore a putative role of the vH ϩ -ATPase in the functional adaptation of the rumen epithelium to a concentrate-supplemented diet. To this purpose, sheep were fed either an ad libitum hay diet (h diet) or a diet consisting of hay ad libitum and additional concentrate (h/c diet).…”

mentioning

confidence: 99%

“…In our previous studies, we characterized rumen vH ϩ -ATPase as an important component for REC pH i regulation (9) and a sensor of substrate and energy availability in vitro (28). Metabolic inhibition (MI) of REC by glucose substitution with 2-deoxyglucose (2-DOG) and/or application of antimycin induced a strong pH i reduction (0.44 Ϯ 0.04 pH units), resulting to about 50% from vH ϩ -ATPase inhibition (28).…”

mentioning

confidence: 99%

“…Metabolic inhibition (MI) of REC by glucose substitution with 2-deoxyglucose (2-DOG) and/or application of antimycin induced a strong pH i reduction (0.44 Ϯ 0.04 pH units), resulting to about 50% from vH ϩ -ATPase inhibition (28). The ruminal vH ϩ -ATPase B subunit shows diffuse cytosolic distribution after MI.…”

mentioning

confidence: 99%

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Modulation of vH⁺-ATPase is part of the functional adaptation of sheep rumen epithelium to high-energy diet

Kuzinski

Žitňan

Albrecht

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Ruminal vacuolar H(+)-ATPase (vH(+)-ATPase) activity is regulated by metabolic signals. Thus, we tested whether its localization, expression, and activity were changed by different feeding. Young male sheep (n = 12) were either fed hay ad libitum (h) or hay ad libitum plus additional concentrate (h/c) for 2 wk. The vH(+)-ATPase B subunit signal was predominantly found in the cell membrane and cytosol of rumen epithelial cells (REC) with basal/parabasal phenotype. The elevated number (threefold) of these cells in rumen mucosa of h/c-fed sheep reflects a high proliferative capacity and, explains the 2.3-fold increase of the total number of vH(+)-ATPase-expressing REC. However, in accordance with a 58% reduction of the vH(+)-ATPase B subunit mRNA expression in h/c-fed sheep, its protein amount per single REC was decreased. Using the fluorescent probe BCECF and selective inhibitors (foliomycin, amiloride), the contribution of vH(+)-ATPase and Na(+)/H(+) exchanger to intracellular pH (pH(i)) regulation was investigated. REC isolated from h/c-fed sheep keep their pH(i) at a significantly higher level (6.91 ± 0.03 vs. 6.74 ± 0.05 in h-fed sheep). Foliomycin or amiloride decreased pH(i) by 0.16 ± 0.02 and 0.57 ± 0.04 pH units when applied to REC from h-fed sheep, but the effects were markedly reduced (-88 and -33%) after concentrate feeding. Nevertheless, we found that REC proliferation rate and [cAMP](i) were reduced after foliomycin-induced vH(+)-ATPase inhibition. Our results provide the first evidence for a role of vH(+)-ATPase in regulation of REC proliferation, most probably by linking metabolically induced pH(i) changes to signaling pathways regulating this process.

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The Vacuolar ATPase – A Nano-scale Motor That Drives Cell Biology

Harrison

Muench

2018

Subcellular Biochemistry

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The vacuolar H-ATPase (V-ATPase) is a ~1 MDa membrane protein complex that couples the hydrolysis of cytosolic ATP to the transmembrane movement of protons. In essentially all eukaryotic cells, this acid pumping function plays critical roles in the acidification of endosomal/lysosomal compartments and hence in transport, recycling and degradative pathways. It is also important in acid extrusion across the plasma membrane of some cells, contributing to homeostatic control of cytoplasmic pH and maintenance of appropriate extracellular acidity. The complex, assembled from up to 30 individual polypeptides, operates as a molecular motor with rotary mechanics. Historically, structural inferences about the eukaryotic V-ATPase and its subunits have been made by comparison to the structures of bacterial homologues. However, more recently, we have developed a much better understanding of the complete structure of the eukaryotic complex, in particular through advances in cryo-electron microscopy. This chapter explores these recent developments, and examines what they now reveal about the catalytic mechanism of this essential proton pump and how its activity might be regulated in response to cellular signals.

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The Vacuolar-TypeH+-ATPase in Ovine Rumen Epithelium is Regulated by Metabolic Signals

Cited by 5 publications

References 74 publications

Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer

Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer

Modulation of vH⁺-ATPase is part of the functional adaptation of sheep rumen epithelium to high-energy diet

The Vacuolar ATPase – A Nano-scale Motor That Drives Cell Biology

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The Vacuolar-TypeH+-ATPase in Ovine Rumen Epithelium is Regulated by Metabolic Signals

Cited by 5 publications

References 74 publications

Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer

Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer

Modulation of vH+-ATPase is part of the functional adaptation of sheep rumen epithelium to high-energy diet

The Vacuolar ATPase – A Nano-scale Motor That Drives Cell Biology

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Modulation of vH⁺-ATPase is part of the functional adaptation of sheep rumen epithelium to high-energy diet