Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis

Quan, Yumeng; Du, Yu; Tong, Yuxin; Gu, Sumin; Jiang, Jean X.

doi:10.3390/antiox10091374

Cited by 14 publications

(15 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An association between connexins, redox potential and oxidative stress is well established ( Quan et al, 2021 ; Zhang et al, 2021 ), although low or physiological levels NO could have a protective effect in lens epithelial cells ( Chamberlain et al, 2008 ). A high production of NO in human lens has been associated with cataracts, especially in hypertensive patients ( Ornek et al, 2003 ) and smokers ( Anitha et al, 2019 ), and a similar association has been found in animal models of hypertension and diabetes ( Abdul Nasir et al, 2017 ; Yadav et al, 2018 ).…”

Section: Cx46 Posttranslational Modifications and Their Potential Rel...mentioning

confidence: 99%

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

Retamal

Altenberg

2022

Front. Physiol.

View full text Add to dashboard Cite

Connexins are a family of proteins that can form two distinct types of channels: hemichannels and gap junction channels. Hemichannels are composed of six connexin subunits and when open allow for exchanges between the cytoplasm and the extracellular milieu. Gap junction channels are formed by head-to-head docking of two hemichannels in series, each one from one of two adjacent cells. These channels allow for exchanges between the cytoplasms of contacting cells. The lens is a transparent structure located in the eye that focuses light on the retina. The transparency of the lens depends on its lack of blood irrigation and the absence of organelles in its cells. To survive such complex metabolic scenario, lens cells express Cx43, Cx46 and Cx50, three connexins isoforms that form hemichannels and gap junction channels that allow for metabolic cooperation between lens cells. This review focuses on the roles of Cx46 hemichannels and gap junction channels in the lens under physiological conditions and in the formation of cataracts, with emphasis on the modulation by posttranslational modifications.

show abstract

Section: Cx46 Posttranslational Modifications and Their Potential Rel...mentioning

confidence: 99%

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

Retamal

Altenberg

2022

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…The permeability and transport properties of these channels are implicated in lens epithelial growth and proliferation, Na + and water coupled transport, Ca 2+ transport, antioxidant gradients, and second messenger permeability ( Mathias et al, 2010 ; Slavi et al, 2014 ; Brink et al, 2020 ). One important nutrient that connexin channels circulate is the tripeptide glutathione (GSH), which is the main alleviator of oxidative stress in lens fiber cells ( Slavi et al, 2014 ; Braakhuis et al, 2019 ; Quan et al, 2021 ). The role of connexin channels in the lens has been primarily established using genetic knock-out (KO) and knock-in (KI) models ( Berthoud et al, 2014 ).…”

Section: The Lens Circulationmentioning

confidence: 99%

“…Age and oxidative stress in the lens are usually coincident and lead to changes in the lens proteome, including connexin channel density and regulation ( Gao et al, 2013 ; Gong et al, 2021 ; Quan et al, 2021 ). The lens is protected from oxidative damage by antioxidants, such as GSH, and chaperone proteins to prevent protein aggregation and dissolution from oxidative stress ( Giblin, 2000 ; Lim et al, 2020 ).…”

Section: Aging and Oxidative Stress Impact The Channels Underlying The Lens Circulationmentioning

confidence: 99%

“…However, the mechanism of how GSSG is removed from the nucleus is still unknown, but is predicted to also work through passive diffusion to the surface cells or breakdown in the nucleus directly ( Slavi et al, 2014 ). Connexin hemichannels opened in response to H 2 O 2 , mechanical stress, or ultraviolet radiation and allowed transit of glucose, GSH, and H 2 O 2 ( Liu et al, 2020 ; Quan et al, 2021 ). These results suggested that connexin hemichannels may also play a key role in maintaining the metabolic and antioxidative function of the lens, through facilitation of direct exchange of nutrients and redox metabolites between the extracellular space and cytoplasm.…”

Section: Aging and Oxidative Stress Impact The Channels Underlying The Lens Circulationmentioning

confidence: 99%

See 1 more Smart Citation

Physiological Mechanisms Regulating Lens Transport

Giannone

Sellitto

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

The transparency and refractive properties of the lens are maintained by the cellular physiology provided by an internal microcirculation system that utilizes spatial differences in ion channels, transporters and gap junctions to establish standing electrochemical and hydrostatic pressure gradients that drive the transport of ions, water and nutrients through this avascular tissue. Aging has negative effects on lens transport, degrading ion and water homeostasis, and producing changes in lens water content. This alters the properties of the lens, causing changes in optical quality and accommodative amplitude that initially result in presbyopia in middle age and ultimately manifest as cataract in the elderly. Recent advances have highlighted that the lens hydrostatic pressure gradient responds to tension transmitted to the lens through the Zonules of Zinn through a mechanism utilizing mechanosensitive channels, multiple sodium transporters respond to changes in hydrostatic pressure to restore equilibrium, and that connexin hemichannels and diverse intracellular signaling cascades play a critical role in these responses. The mechanistic insight gained from these studies has advanced our understanding of lens transport and how it responds and adapts to different inputs both from within the lens, and from surrounding ocular structures.

show abstract

“…Substantial evidence has shown that aggravated oxidative stress in the lens epithelial cells (LECs) layer is a vital initiation factor in cataract formation 5 . Previous studies have also indicated that exposure to environmental risk factors produces reactive oxygen species (ROS) which can disrupt the redox balance of LECs 6 resulting in oxidation of lens proteins, DNA damage and/or lipid peroxidation, all of which have been implicated in formation lens opacity 7…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin‐1 regulates the autophagy induced by oxidative stress through LC3‐II in human lens epithelial cells

Liu

Chen

et al. 2023

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Oxidative stress plays a major role in age‐related cataract development. The cellular antioxidant protein thioredoxin‐1 (Trx‐1) and its negative regulator, thioredoxin binding protein‐2 (TBP‐2), are pivotal in the cellular redox balance during oxidative stress. The aim of this study is to investigate the effect of Trx‐1 and TBP‐2 on LC3 I/LC3 II in oxidative stress‐induced autophagy in human lens epithelial cells (LECs). In our study, LECs were treated with 50 μM H2O2 for different durations, and the expression of Trx‐1 and TBP‐2 were measured by RT‐PCR and Western blot. Trx‐1 activity was evaluated by the thioredoxin activity fluorescent assay. The subcellular localization of Trx‐1 and TBP‐2 was evaluated by cellular immunofluorescence. The interaction between Trx‐1 and TBP‐2 was examined by co‐immunoprecipitation. The cell viability was detected using CCK‐8, and the expression of LC3‐II/LC3‐I was detected to evaluate the autophagy. The results showed that the mRNA levels of the Trx‐1 and TBP‐2 were kinetically changed after treatment with H2O2 for different durations. Exposure to H2O2 increased the expression of TBP‐2 but not Trx‐1, while the exposure inhibited Trx‐1 activity. TBP‐2 was co‐localized with Trx‐1, and exposure to H2O2 increased the interaction between TBP‐2 and Trx‐1. Trx‐1 overexpression enhanced the autophagic response under normal circumstances and it might regulate autophagy in the initial phase. This study demonstrates the differential role of Trx‐1 in cellular oxidative stress response, oxidative stress increased Trx‐1 interaction with TBP‐2, and Trx‐1/TBP‐2 regulated the autophagic response in the initial phase through LC3‐II.

show abstract

Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis

Cited by 14 publications

References 151 publications

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

Role and Posttranslational Regulation of Cx46 Hemichannels and Gap Junction Channels in the Eye Lens

Physiological Mechanisms Regulating Lens Transport

Thioredoxin‐1 regulates the autophagy induced by oxidative stress through LC3‐II in human lens epithelial cells

Contact Info

Product

Resources

About