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Pflugers Arch
2011 Jun 01;4616:635-43. doi: 10.1007/s00424-011-0936-3.
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Biphasic effect of linoleic acid on connexin 46 hemichannels.
Retamal MA
,
Evangelista-Martínez F
,
León-Paravic CG
,
Altenberg GA
,
Reuss L
.
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Connexins form hemichannels at undocked plasma membranes and gap-junction channels (GJCs) at intercellular contacting zones. Under physiological conditions, hemichannels have low open probabilities, but their activation under pathological conditions, such as ischemia, induces and/or accelerates cell death. Connexin 46 (Cx46) is a major connexin of the lens, and mutations of this connexin induce cataracts. Here, we report the effects of linoleic acid (LA) on the electrical properties of Cx46 GJCs and hemichannels expressed in Xenopus laevis oocytes. LA has a biphasic effect, increasing hemichannel current at 0.1 μM and decreasing it at concentrations of 100 μM or higher. The effects of extracellular and microinjected LA conjugated to coenzyme A (LA-CoA) suggest that the current activation site is accessible from the intracellular but not extracellular compartment, whereas the current inhibitory site is either located in a region of the hemichannel pore inaccessible to intracellular LA-CoA, or requires crossing of LA through an organelle membrane. Experiments with other fatty acids demonstrated that the block of hemichannels depends on the presence of a hydrogenated double bond at position 9 and is directly proportional to the number of double bonds. Experiments in paired oocytes expressing Cx46 showed that LA does not affect GJCs. The block by unsaturated fatty acids reported here opens the possibility that increases in the concentration of these lipids in the lens induce cataract formation by blocking Cx46 hemichannels.
Anel,
Membrane partition of fatty acids and inhibition of T cell function.
1993, Pubmed
Anel,
Membrane partition of fatty acids and inhibition of T cell function.
1993,
Pubmed
Bao,
Mechanism of regulation of the gap junction protein connexin 43 by protein kinase C-mediated phosphorylation.
2004,
Pubmed
,
Xenbase
Beahm,
Opening hemichannels in nonjunctional membrane stimulates gap junction formation.
2004,
Pubmed
,
Xenbase
Berthoud,
Oxidative stress, lens gap junctions, and cataracts.
2009,
Pubmed
Besancon,
Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke.
2008,
Pubmed
Beyer,
Antisera directed against connexin43 peptides react with a 43-kD protein localized to gap junctions in myocardium and other tissues.
1989,
Pubmed
Boger,
Chemical requirements for inhibition of gap junction communication by the biologically active lipid oleamide.
1998,
Pubmed
Borenshtein,
Cataract development in diabetic sand rats treated with alpha-lipoic acid and its gamma-linolenic acid conjugate.
2001,
Pubmed
Boylan,
Interactions of acyl-coenzyme A with phosphatidylcholine bilayers and serum albumin.
1992,
Pubmed
Bruzzone,
Connexin 43 hemi channels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells.
2001,
Pubmed
Cascio,
Connexins and their environment: effects of lipids composition on ion channels.
2005,
Pubmed
Cherian,
Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin.
2005,
Pubmed
Clarke,
Site of action of fatty acids and other charged lipids on BKCa channels from arterial smooth muscle cells.
2003,
Pubmed
Clarke,
Modulation of BK(Ca) channel activity by fatty acids: structural requirements and mechanism of action.
2002,
Pubmed
Denson,
Effects of fatty acids on BK channels in GH(3) cells.
2000,
Pubmed
Ebihara,
Properties of connexin 46 hemichannels in dissociated lens fiber cells.
2011,
Pubmed
,
Xenbase
El-Yassimi,
Linoleic acid induces calcium signaling, Src kinase phosphorylation, and neurotransmitter release in mouse CD36-positive gustatory cells.
2008,
Pubmed
Feng,
Reduction in voltage-gated K+ currents in primary cultured rat pancreatic beta-cells by linoleic acids.
2006,
Pubmed
Fleschner,
Connexin 46 and connexin 50 in selenite cataract.
2006,
Pubmed
Fraser,
Changes in plasma free fatty acid concentrations in rheumatoid arthritis patients during fasting and their effects upon T-lymphocyte proliferation.
1999,
Pubmed
Glanz,
Fatty acid cytotoxicity to organ-cultured bovine lenses.
2006,
Pubmed
Gong,
Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice.
1997,
Pubmed
Goodenough,
Lens gap junctions: a structural hypothesis for nonregulated low-resistance intercellular pathways.
1979,
Pubmed
Hamilton,
Molecular localization of the inhibitory arachidonic acid binding site to the pore of hIK1.
2003,
Pubmed
Hirschi,
Oleic acid differentially affects gap junction-mediated communication in heart and vascular smooth muscle cells.
1993,
Pubmed
Hopperstad,
Properties of gap junction channels formed by Cx46 alone and in combination with Cx50.
2000,
Pubmed
Iwig,
Fatty acid cytotoxicity to human lens epithelial cells.
2004,
Pubmed
Jahn,
Lipid composition of human aqueous humor.
1983,
Pubmed
Kamp,
pH gradients across phospholipid membranes caused by fast flip-flop of un-ionized fatty acids.
1992,
Pubmed
Kangani,
New method for GC/FID and GC-C-IRMS analysis of plasma free fatty acid concentration and isotopic enrichment.
2008,
Pubmed
Kim,
Linoleic acid induces mouse embryonic stem cell proliferation via Ca2+/PKC, PI3K/Akt, and MAPKs.
2009,
Pubmed
Kistler,
Identification of a 70,000-D protein in lens membrane junctional domains.
1985,
Pubmed
Kojima,
[The opacity of the rat lens caused by fatty acid peroxide].
1968,
Pubmed
KRONFELD,
Eye changes due to advanced age.
1953,
Pubmed
Lo,
Gap junction structures and distribution patterns of immunoreactive connexins 46 and 50 in lens regrowths of Rhesus monkeys.
1996,
Pubmed
Locke,
Connexin channels and phospholipids: association and modulation.
2009,
Pubmed
Lu,
Dietary fat intake and early age-related lens opacities.
2005,
Pubmed
Mathias,
Physiological properties of the normal lens.
1997,
Pubmed
Matta,
TRPV1 is a novel target for omega-3 polyunsaturated fatty acids.
2007,
Pubmed
,
Xenbase
Nguyen,
Fatty acid cytotoxicity to bovine lens epithelial cells: investigations on cell viability, ecto-ATPase, Na(+), K(+)-ATPase and intracellular sodium concentrations.
2000,
Pubmed
Nojima,
Oleamide derivatives are prototypical anti-metastasis drugs that act by inhibiting Connexin 26.
2007,
Pubmed
Oliveira,
Mechanism of modulation of the plasma membrane Ca(2+)-ATPase by arachidonic acid.
2008,
Pubmed
Pal,
Connexin46 mutations linked to congenital cataract show loss of gap junction channel function.
2000,
Pubmed
,
Xenbase
Pal,
Molecular mechanism underlying a Cx50-linked congenital cataract.
1999,
Pubmed
,
Xenbase
Paul,
Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Retamal,
Voltage-dependent facilitation of Cx46 hemichannels.
2010,
Pubmed
,
Xenbase
Retamal,
Modulation of Cx46 hemichannels by nitric oxide.
2009,
Pubmed
,
Xenbase
Retamal,
Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia.
2007,
Pubmed
Roberts-Crowley,
Arachidonic acid inhibition of L-type calcium (CaV1.3b) channels varies with accessory CaVbeta subunits.
2009,
Pubmed
Sáez,
Cell membrane permeabilization via connexin hemichannels in living and dying cells.
2010,
Pubmed
Schalper,
Connexin hemichannel composition determines the FGF-1-induced membrane permeability and free [Ca2+]i responses.
2008,
Pubmed
Schmitz,
The opposing effects of n-3 and n-6 fatty acids.
2008,
Pubmed
STEINBERG,
Metabolism of essential fatty acids. IV. Incorporation of linoleate into arachidonic acid.
1956,
Pubmed
Stout,
Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels.
2002,
Pubmed
Stridh,
Stimulated efflux of amino acids and glutathione from cultured hippocampal slices by omission of extracellular calcium: likely involvement of connexin hemichannels.
2008,
Pubmed
Tan,
Influence of diabetes and cardiovascular disease on the long-term incidence of cataract: the Blue Mountains eye study.
2008,
Pubmed
Trimborn,
Linoleic acid cytotoxicity to bovine lens epithelial cells: influence of albumin on linoleic acid uptake and cytotoxicity.
2000,
Pubmed
Ye,
Functional hemichannels in astrocytes: a novel mechanism of glutamate release.
2003,
Pubmed
