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Connexin Cell Communication Channels: Roles in the Immune System and Immunopathology

2013 Edition, March 22, 2013

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ISBN: 978-1-4398-6257-5
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Product Details:

  • Revision: 2013 Edition, March 22, 2013
  • Published Date: March 22, 2013
  • Status: Active, Most Current
  • Document Language: English
  • Published By: CRC Press (CRC)
  • Page Count: 370
  • ANSI Approved: No
  • DoD Adopted: No

Description / Abstract:

Preface

Cells.collaborate.and.communicate,.working.as.a.team..This.is.especially.evident.in. our.tissues.and.organs..The.key.proteins.acting.as.membrane.channels.that.enable. direct.communication.or.cross. talk.between. attached.cells.are.connexins. (Cxs),. a. family. of. around. 22. closely. homologous. proteins. in. vertebrates. that. oligomerize. generating.a.hexameric.arrangement.in.the.membrane.with.a.central.pore..Aligned. head.to.head,.groups.of.these.Cx.hemichannels.form.a.gap.junction-a.well-established. structure.that.provides.a.conduit.connecting.directly.cell.interiors.

An.important.and.surprising.finding.in.the.cell.communication/signalling.field. has. been.widespread. detection. of. functional.Cx. channels. in. cells. comprising. the. immune.system..Morphologically.mature.gap.junctions.are.rarely.recognized.in.the. immune.system.except.in.lymphoid.tissues,.and.intensive.recent.research.has.pointed. to.the.functional.roles.of.Cx.hemichannels.residing.in.the.cell's.plasma.membrane.. Normally.closed,.these.hemichannels.when.they.become.leaky.present.cells.with.a. severe.metabolic.disability.as.they.lose.control.of.the.dynamics.between.the.cytoplasm. and.the.surrounding.milieu..Environmental.insults.such.as.hypoxia,.oxidative,. osmotic,.and.mechanical.stresses.can.provide.challenges.to.the gating.integrity.of. hemichannels.as.they.become.permeable.for.example,.allowing,.the.leakage.of.ATP. and.glutamate..In. the. immune. system. especially. the. loss. of.purinergic.molecules. poses.signalling.problems.and.can.modify.the.interaction.of.not.only.immune.cells. but.also.with.endothelial.and.other.cells.depending.on.location.

The.identification.of.Cx.hemichannels,.especially.those.built.up.of.Cx43,.as.key. cell. communication. regulators. and. their. easy. accessibility. to. direct. modulation. by."chemical.blockage".has.opened.up.the.field.to.an.ever-increasing.translational. applications.and.these.are.described.in.specific.chapters..A.wide.range.of."mimetic. peptide".reagents.are.finding.potentially.important.applications.in.diseases.induced. by.hypoxia.in.the.brain.and.cardiovascular.systems..Also,.the.use.of.antisense.RNA. reagents.provides.an.alternative.and.complementary.way.of.addressing.the.consequences. of.Cx.channel.dysfunction.in.several.diseases.as.illustrated.in.many.chapters. and.especially.in.relation.to.diabetes..The.development.of.peptide.mimetics.that. confine.their.targeting.to.hemichannels.and.avoid.deleterious.action.on.gap.junction. functions.(e.g.,.as.in.addressing.cardiac.arrhythmia.as.opposed.to.hypoxic.damage). are.on.the.horizon.and.will.provide.an.added.level.of.selectivity.in.targeting.hemichannels.. These.can.aid.in.dissecting.the.physiological.and.pathological.roles.of.Cx. channels.especially.in.the.immune.system.itself.and.in.lymphoid.cells.and.organs.. Finally,.the.implication.of.pannexin.(Panx).channels.similar.younger.but.unrelated. cousins.of.the.Cx.hemichannels.are.considered.by.various.authors.

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