Blockade of plasma membrane calcium pumping ATPase isoform I impairs nerve growth factor-induced neurite extension in pheochromocytoma cells

Brandt, Paul; Sisken, Jesse E.; Neve, Rachael L.; Vanaman, Thomas C.

doi:10.1073/pnas.93.24.13843

Cited by 34 publications

(33 citation statements)

References 31 publications

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“…Stable antisense approaches have been used previously by others to study the functional role of PMCA. For instance, inhibition of PMCA1 expression in PC6 pheochromocytoma cells via stable antisense hinders neuronal differentiation and neurite extension in response to nerve growth factor (38). A tetracycline-regulated approach to antisense expression possesses advantages over the use of antisense oligonucleotides or transient siRNA transfection.…”

Section: Plasma Membrane Camentioning

confidence: 99%

Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Lee

Robinson

Holman

et al. 2005

Journal of Biological Chemistry

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Alterations in Ca2؉ signaling may contribute to tumorigenesis and the mechanism of action of some anticancer drugs. The plasma membrane calcium-ATPase (PMCA) is a crucial controller of intracellular Ca 2؉ signaling. Altered PMCA expression occurs in the mammary gland during lactation and in breast cancer cell lines. Despite this, the consequences of PMCA inhibition in breast cancer cell lines have not been investigated. In this work, we used Tet-off PMCA antisense-expressing MCF-7 cells to assess the effects of PMCA inhibition in a human breast cancer cell line. At a level of PMCA inhibition that did not completely prevent PMCA-mediated Ca 2؉ efflux and did not induce cell death, a dramatic inhibition of cellular proliferation was observed. Fluorescence-activated cell sorting analysis indicated that PMCA antisense involves changes in cell cycle kinetics but not cell cycle arrest. We concluded that modulation of PMCA has important effects in regulating the proliferation of human breast cancer MCF-7 cells.

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Section: Plasma Membrane Camentioning

confidence: 99%

Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Lee

Robinson

Holman

et al. 2005

Journal of Biological Chemistry

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“…For example, blockade of PMCA 1 causes no change in the levels of resting free [Ca 2+ ]i or its release from intracellular stores but results in a significantly slower rate of Ca 2+ clearance following release from intracellular stores [80] . However, the most striking effect of lowered PMCA 1 in PC6 cells is the impairment in neurite extension elicited by nerve growth factor (NGF) [80] . Cells with reduced PMCA 1 levels have fewer and shorter neurites and a conspicuous absence of defined growth cones in response to NGF.…”

Section: Pmca Expressionmentioning

confidence: 99%

“…PMCA activity is significantly reduced in response to cellular cholesterol depletion suggesting the possibility of local regulation of the pump activity in lipid rafts [78] . Antisense-(AS) plasmid-mediated reduction of specific isoforms has yielded valuable information on the role of individual PMCA subtypes in regulating the dynamics of cellular Ca 2+ handling and also their contribution to a diverse array of neuronal functions [80][81][82][83][84] . For example, blockade of PMCA 1 causes no change in the levels of resting free [Ca 2+ ]i or its release from intracellular stores but results in a significantly slower rate of Ca 2+ clearance following release from intracellular stores [80] .…”

Section: Pmca Expressionmentioning

confidence: 99%

“…Antisense-(AS) plasmid-mediated reduction of specific isoforms has yielded valuable information on the role of individual PMCA subtypes in regulating the dynamics of cellular Ca 2+ handling and also their contribution to a diverse array of neuronal functions [80][81][82][83][84] . For example, blockade of PMCA 1 causes no change in the levels of resting free [Ca 2+ ]i or its release from intracellular stores but results in a significantly slower rate of Ca 2+ clearance following release from intracellular stores [80] . However, the most striking effect of lowered PMCA 1 in PC6 cells is the impairment in neurite extension elicited by nerve growth factor (NGF) [80] .…”

Section: Pmca Expressionmentioning

confidence: 99%

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Plasma membrane Ca²⁺-ATPases: Targets of oxidative stress in brain aging and neurodegeneration

Zaidi¹

2010

WJBC

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The plasma membrane Ca 2+ -ATPase (PMCA) pumps play an important role in the maintenance of precise levels of intracellular Ca 2+ [Ca 2+ ]i, essential to the functioning of neurons. In this article, we review evidence showing age-related changes of the PMCAs in synaptic plasma membranes (SPMs). PMCA activity and protein levels in SPMs diminish progressively with increasing age. The PMCAs are very sensitive to oxidative stress and undergo functional and structural changes when exposed to oxidants of physiological relevance. The major signatures of oxidative modification in the PMCAs are rapid inactivation, conformational changes, aggregation, internalization from the plasma membrane and proteolytic degradation. PMCA proteolysis appears to be mediated by both calpains and caspases. The predominance of one proteolytic pathway vs the other, the ensuing pattern of PMCA degradation and its consequence on pump activity depends largely on the type of insult, its intensity and duration. Experimental reduction of PMCA expression not only alters the dynamics of cellular Ca 2+ handling but also has a myriad of downstream consequences on various aspects of cell function, indicating a broad role of these pumps. Age-and oxidation-related down-regulation of the PMCAs may play an important role in compromised neuronal function in the aging brain and its several-fold increased susceptibility to neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and stroke. Therapeutic approaches that protect the PMCAs and stabilize [Ca 2+ ]i homeostasis may be capable of slowing and/or preventing neuronal degeneration. The PMCAs are therefore emerging as a new class of drug targets for therapeutic interventions in various chronic degenerative disorders.

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“…Furthermore, antisense/sense approaches have been used in PC12 cells to examine the in vivo functions of a wide variety of neuronal proteins including (12), GAP-43 or neuromodulin (13)(14)(15)(16), the ␣ subunit of G o (17), calmodulin-dependent protein kinase II (18), annexin II (19), and the plasma membrane calcium ATPase pump (20). To determine if S100A1 regulates cytoskeletal organization in neuronal cells, we have examined the effects of ablated S100A1 expression on ␣-tubulin levels in PC12 cells as well as the number and length of neurites extended by PC12 cells in response to NGF.…”

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confidence: 99%

S100A1 Regulates Neurite Organization, Tubulin Levels, and Proliferation in PC12 Cells

Zimmer

Cornwall

Reynolds

et al. 1998

Journal of Biological Chemistry

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As a first step in determining what cellular processes are regulated by the calcium-modulated protein S100A1 isoform in neurons, the effects of ablated S100A1 expression on neurite organization and microtubule/tubulin levels in PC12 cells were examined. A mammalian expression vector containing the rat S100A1 cDNA in the antisense orientation with respect to a cytomegalovirus promoter was constructed and transfected into PC12 cells. Indirect immunofluorescence microscopy confirmed decreased S100A1 protein levels in all three stable transfectants (pAntisense clones) that expressed exogenous S100A1 antisense mRNA. In response to nerve growth factor, pAntisense clones extended significantly more neurites than control cells (4.01 ؎ 0.16 versus 2.93 ؎ 0.16 neurites/cell). This increase in neurite number was accompanied by an increase in total ␣-tubulin levels in untreated (4.0 ؎ 0.6 versus 1.76 ؎ 0.4 ng of ␣-tubulin/mg of total protein) and nerve growth factortreated pAntisense clones (4.15 ؎ 0.4 versus 2.04 ؎ 0.5 ng of ␣-tubulin/mg of total protein) when compared with control cells. At high cell densities, pAntisense clones exhibited a significant decrease in anchorage-dependent growth. In soft agar, pAntisense clones formed significantly more colonies (153 ؎ 8%) than control cells (116 ؎ 5%). However, the pAntisense soft agar colonies were significantly smaller than those observed in control cells (40.6 ؎ 3.0 versus 59.5 ؎ 1.2 m). These data suggest that cell density inhibits both anchorage-independent and -dependent growth of pAntisense clones. In summary, ablation of S100A1 expression in PC12 cells results in increased tubulin levels, altered neurite organization, and decreased cell growth. Thus, S100A1 may directly link the cytoskeleton and calcium signal transduction pathways to cell proliferation.The S100 protein family is a group of calcium-binding proteins that exhibit a high degree of conservation in amino acid sequence, secondary structure, and genomic organization (1-3). To date, there are 18 members of the S100 family, 13 of which are clustered in region q21 of human chromosome 1 (see Refs. 4 and 5). A new nomenclature that reflects the genomic organization of these proteins has recently been adopted, and S100␣ is now designated S100A1 and S100␤ is designated S100B (6). S100A1 and S100B were the original members of this family and have been implicated in a diverse group of cellular functions including cell-cell communication, cell growth, cell structure, energy metabolism, contraction, and intracellular calcium signal transduction (see Refs. 1 and 3).Because each S100 monomer contains two EF-hand high affinity calcium binding domains, they have been included in the S100-troponin-calmodulin superfamily of calcium-modulated proteins. These proteins have no known enzymatic activity and function by modulating the activity of other proteins termed target proteins. Calmodulin appears to be the "workhorse" in calcium signaling and to be responsible for generating the main events triggered by changes in intracell...

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Blockade of plasma membrane calcium pumping ATPase isoform I impairs nerve growth factor-induced neurite extension in pheochromocytoma cells

Cited by 34 publications

References 31 publications

Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Plasma membrane Ca²⁺-ATPases: Targets of oxidative stress in brain aging and neurodegeneration

S100A1 Regulates Neurite Organization, Tubulin Levels, and Proliferation in PC12 Cells

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Blockade of plasma membrane calcium pumping ATPase isoform I impairs nerve growth factor-induced neurite extension in pheochromocytoma cells

Cited by 34 publications

References 31 publications

Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Antisense-mediated Inhibition of the Plasma Membrane Calcium-ATPase Suppresses Proliferation of MCF-7 Cells

Plasma membrane Ca2+-ATPases: Targets of oxidative stress in brain aging and neurodegeneration

S100A1 Regulates Neurite Organization, Tubulin Levels, and Proliferation in PC12 Cells

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Plasma membrane Ca²⁺-ATPases: Targets of oxidative stress in brain aging and neurodegeneration