Cell Swelling Activates Phospholipase A 2 in Ehrlich Ascites Tumor Cells

Thoroed, S. M.; Lauritzen, Lotte; Lambert, Ian Henry; Hansen, Harald S.; Hoffmann, Else K.

doi:10.1007/s002329900294

Cited by 69 publications

(57 citation statements)

References 34 publications

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“…First, it has been demonstrated in a number of cell types that cell swelling leads to the activation of PLA 2 , resulting in the release of polyunsaturated fatty acids, including AA, from membrane phospholipids (26)(27)(28). Second, we found recently that AA acts as a potent activator of TRPV4 (22).…”

Section: Discussionmentioning

confidence: 84%

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Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4

Vriens

Watanabe

Janssens

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

576

532

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TRPV4 is a Ca 2؉ -and Mg 2؉ -permeable cation channel within the vanilloid receptor subgroup of the transient receptor potential (TRP) family, and it has been implicated in Ca 2؉ -dependent signal transduction in several tissues, including brain and vascular endothelium. TRPV4-activating stimuli include osmotic cell swelling, heat, phorbol ester compounds, and 5 ,6 -epoxyeicosatrienoic acid, a cytochrome P450 epoxygenase metabolite of arachidonic acid (AA). It is presently unknown how these distinct activators converge on opening of the channel. Here, we demonstrate that blockers of phospholipase A 2 (PLA2) and cytochrome P450 epoxygenase inhibit activation of TRPV4 by osmotic cell swelling but not by heat and 4␣-phorbol 12,13-didecanoate. Mutating a tyrosine residue (Tyr-555) in the N-terminal part of the third transmembrane domain to an alanine strongly impairs activation of TRPV4 by 4␣-phorbol 12,13-didecanoate and heat but has no effect on activation by cell swelling or AA. We conclude that TRPV4-activating stimuli promote channel opening by means of distinct pathways. Cell swelling activates TRPV4 by means of the PLA 2-dependent formation of AA, and its subsequent metabolization to 5 ,6 -epoxyeicosatrienoic acid by means of a cytochrome P450 epoxygenase-dependent pathway. Phorbol esters and heat operate by means of a distinct, PLA 2-and cytochrome P450 epoxygenase-independent pathway, which critically depends on an aromatic residue at the N terminus of the third transmembrane domain.T he TRPV subfamily of the transient receptor potential (TRP) family of cation channels consists of at least six mammalian channels homologous to the vanilloid receptor (for a unifying nomenclature, see ref. 1). The TRPV channels are activated by a variety of signals, including chemical and thermal stimuli, cell swelling, low intracellular Ca 2ϩ , and endogenous or synthetic ligands (2-10). Members of this subfamily contain a hydrophobic core region comprising six putative transmembrane segments (TM1-TM6), a pore-loop region between TM5 and TM6, a cytoplasmic N terminus with three to six ankyrin repeats, and a cytoplasmic C terminus (1, 3). The TRPV subfamily can be subdivided into two groups. One group is formed by TRPV1-TRPV4, which display a moderate Ca 2ϩ selectivity (P Ca ͞P Na Ͻ 10, in which P is permeability), a weak field-strength monovalent cation permeability sequence, and steep temperature dependence (5,6,(11)(12)(13)(14)(15)(16). The second group is formed by TRPV5 and TRPV6, which are highly Ca 2ϩ selective (P Ca ͞P Na Ͼ 100) and display a permeability sequence for monovalent cations consistent with a strong field-strength binding site but show little temperature dependence (10,17,18).TRPV4 was identified originally as a channel activated by hypotonic cell swelling (11,13,19), but later reports show that it can be activated also by synthetic agonists, such as the phorbol ester 4␣-phorbol 12,13-didecanoate (4␣-PDD) (5), temperatures Ͼ27°C (6, 20), and acidic pH and citrate (ref. 21; see also ref. 5). Moreover, rec...

show abstract

Section: Discussionmentioning

confidence: 84%

“…Cell swelling has been demonstrated to activate PLA 2 in several cell types (26)(27)(28). Given that PLA 2 activity causes release of fatty acids from membrane phospholipids, we asked whether swelling-induced activation of TRPV4 might occur by means of PLA 2 -dependent release of AA.…”

Section: Hypotonicity-induced Activation Of Trpv4 Is Not Mediated By mentioning

confidence: 99%

Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4

Vriens

Watanabe

Janssens

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

576

532

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“…LPC is produced after osmotic cell swelling (41) and during ischemia (39). Shaik and Downar (39) reported a 60% increase in LPC levels, from 14 to 23 M, after 8 min of ischemia in the myocardium.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species are important mediators of taurine release from skeletal muscle cells

Ørtenblad

Young

Oksbjerg

et al. 2003

American Journal of Physiology-Cell Physiology

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The present study illustrates elements of the signal cascades involved in the activation of taurine efflux pathways in myotubes derived from skeletal muscle cells. Exposing primary skeletal muscle cells, loaded with 14C-taurine, to 1) hypotonic media, 2) the phospholipase A2 (PLA2) activator melittin, 3) anoxia, or 4) lysophosphatidyl choline (LPC) causes an increase in 14C-taurine release and a concomitant production of reactive oxygen species (ROS). The antioxidants butulated hydroxy toluene and vitamin E inhibit the taurine efflux after cell swelling, anoxia, and addition of LPC. The muscle cells possess two separate taurine efflux pathways, i.e., a swelling- and melittin-induced pathway that requires 5-lipoxygenase activity for activation and a LPC-induced pathway. The two pathways are distinguished by their opposing sensitivity toward the anion channel blocker DIDS and cholesterol. These data provide evidence for PLA2 products and ROS as key mediators of the signal cascade leading to taurine efflux in muscle.

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“…B) PLA 2 IN CELL VOLUME REGULATION. PLA 2 -mediated hydrolysis of phospholipids to free fatty acids and lysophospholipids has been demonstrated to be an essential event in the swelling-induced signaling cascade that leads to osmolyte release in a variety of cell types, including EAT cells (989), human platelets (620), mudpuppy RBCs (566), CHP-100 neuroblastoma cells (47), HeLa cells (504), and NIH3T3 cells (492,503,800). Addition of the bee venom melittin, which increases the substrate availability for the PLA 2 (104), stimulates arachidonic acid mobilization (compare Fig.…”

Section: Plamentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,307

1,677

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The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K+, Cl−, and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na+/H+exchange, Na+-K+-2Cl−cotransport, and Na+channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca2+, protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.

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Cell Swelling Activates Phospholipase A 2 in Ehrlich Ascites Tumor Cells

Cited by 69 publications

References 34 publications

Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4

Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4

Reactive oxygen species are important mediators of taurine release from skeletal muscle cells

Physiology of Cell Volume Regulation in Vertebrates

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