ArticleThe Journal of biological chemistry2014
Connexin 46 (cx46) gap junctions provide a pathway for the delivery of glutathione to the lens nucleus.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- A metastasis-associated pannexin-1 mutant (Panx1The FEBS journal · 2025Article
- Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?Antioxidants (Basel, Switzerland) · 2024Review
- Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract.Antioxidants (Basel, Switzerland) · 2024Review
- Mechano-activated connexin hemichannels and glutathione transport protect lens fiber cells against oxidative insults.Redox biology · 2024Article
- Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein.Biomolecules · 2023Review
- The Role of Gap Junctions Dysfunction in the Development of Cataracts: From Loss of Cell-to-Cell Transfer to Blurred Vision-Review.Bioelectricity · 2023Review
- Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway.Nutrients · 2023Review
- Patch clamp studies on TRPV4-dependent hemichannel activation in lens epithelium.Frontiers in pharmacology · 2023Article
- Oxidation of active cysteines mediates protein aggregation of S10R, the cataract-associated mutant of mouse GammaB-crystallin.Proteins · 2022Article
- Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens.Frontiers in physiology · 2022Review
- Redox chemistry of lens crystallins: A system of cysteines.Experimental eye research · 2021Review
- Connexin hemichannels regulate redox potential via metabolite exchange and protect lens against cellular oxidative damage.Redox biology · 2021Article
- Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis.Antioxidants (Basel, Switzerland) · 2021Review
- The mutual interplay of redox signaling and connexins.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Development of a potent embryonic chick lens model for studying congenital cataracts in vivo.Communications biology · 2021Article
- Physiological Mechanisms Regulating Lens Transport.Frontiers in physiology · 2021Review
- Mechanosensitive collaboration between integrins and connexins allows nutrient and antioxidant transport into the lens.The Journal of cell biology · 2020Article
- Regulation of Connexin Gap Junctions and Hemichannels by Calcium and Calcium Binding Protein Calmodulin.International journal of molecular sciences · 2020Review
- Do Connexin Mutants Cause Cataracts by Perturbing Glutathione Levels and Redox Metabolism in the Lens?Biomolecules · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Maintenance of adequate levels of glutathione (GSH) in the lens nucleus is critical for protection of lens proteins from the effects of oxidative stress and for lens transparency. How GSH is transported to the nucleus is unknown. We show that GSH diffuses to the nucleus from the outer cortex, where a high concentration of the anti-oxidant is established by synthesis or uptake, via the network of gap junctions. Using electrophysiological measurements, we found that channels formed by Cx46 and Cx50, the two connexin isoforms expressed in the lens, were moderately cation-selective (P(Na)/P(Cl) ∼5 for Cx46 and ∼3 for Cx50). Single channel permeation of the larger GSH anion was low but detectable (P(Na)/P(GSH) ∼12 for Cx46 and ∼8 for Cx50), whereas permeation of divalent anion glutathione disulfide (GSSG) was undetectable. Measurement of GSH levels in the lenses from connexin knock-out (KO) mice indicated Cx46, and not Cx50, is necessary for transport of GSH to the core. Levels of GSH in the nucleus were markedly reduced in Cx46 KO, whereas they were unaffected by Cx50 KO. We also show that GSH delivery to the nucleus is not dependent on the lens microcirculation, which is believed to be responsible for extracellular transport of other nutrients to membrane transporters in the core. These results indicate that glutathione diffuses from cortical fiber cells to the nucleus via gap junction channels formed by Cx46. We present a model of GSH diffusion from outer cells to inner fiber cells through gap junctions.
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