Connexin hemichannels mediate glutathione transport and protect lens fiber cells from oxidative stress

Journal of Cell Science
Wen ShiJean X Jiang

Abstract

Elevated oxidized stress contributes to lens cataracts, and gap junctions play important roles in maintaining lens transparency. As well as forming gap junctions, connexin (Cx) proteins also form hemichannels. Here, we report a new mechanism whereby hemichannels mediate transport of reductant glutathione into lens fiber cells and protect cells against oxidative stress. We found that Cx50 (also known as GJA8) hemichannels opened in response to H2O2 in lens fiber cells but that transport through the channels was inhibited by two dominant-negative mutants in Cx50, Cx50P88S, which inhibits transport through both gap junctions and hemichannels, and Cx50H156N, which only inhibits transport through hemichannels and not gap junctions. Treatment with H2O2 increased the number of fiber cells undergoing apoptosis, and this increase was augmented with dominant-negative mutants that disrupted both hemichannels formed from Cx46 (also known as GJA3) and Cx50, while Cx50E48K, which only impairs gap junctions, did not have such an effect. Moreover, hemichannels mediate uptake of glutathione, and this uptake protected lens fiber cells against oxidative stress, while hemichannels with impaired transport had less protective benefit from glutathion...Continue Reading

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Citations

Aug 29, 2020·Translational Vision Science & Technology·Bo LiJulie C Lim
Jun 25, 2019·Frontiers in Physiology·Emilia Boiadjieva KnöpfelBarbara Kloeckener-Gruissem
Nov 4, 2020·Pigment Cell & Melanoma Research·Viviana P OrellanaMauricio A Retamal
Nov 6, 2020·International Journal of Molecular Sciences·Zhengping HuJean X Jiang
Dec 17, 2020·Biomolecules·Erin E Mulkearns-HubertJustin D Lathia
Apr 4, 2021·International Journal of Molecular Sciences·Raf Van CampenhoutMathieu Vinken
May 1, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kai ZhangXiao-Yuan Mao

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