Expression and function of connexin 43 protein in mouse and human retinal pigment epithelial cells as hemichannels and gap junction proteins

Akanuma, Shin Ichi; Higashi, Hideyuki; Maruyama, Souhei; Murakami, Koji; Tachikawa, Masanori; Kubo, Yoshiyuki; Hosoya, Ken

doi:10.1016/j.exer.2018.01.016

Cited by 15 publications

(28 citation statements)

References 45 publications

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“…It was found that tight junctions, adherent junctions, and gap junctions were primarily located in the apical lateral intercellular membrane and were close to each other. This result is consistent with the observation by Akanuma et al 4 that connexin 43 was sporadically expressed and colocalized with ZO-1 and N-cadherin in the apical lateral intercellular membrane in mouse and human RPE cells via IF staining. Here, by utilizing immunofluorescence staining in the mouse RBCC, we observed more abundant connexin 43 expression, which colocalized with both E-cadherin and ZO-1 in the intercellular membranes of mouse RPE cells.…”

Section: Discussionsupporting

confidence: 93%

“…Like those in most epithelial cells, the primary cell-cell contacts of RPE cells consist of adherent junctions, 5 gap junctions, 4 and tight junctions. 1 The primary molecular component of each of these three types of junctions is Ecadherin, ZO-1, and connexin 43, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with RPE at the edges of culture sheets, RPE with complete cell-cell contact cannot be activated by TGF-b2 or undergo epithelial-mesenchymal transition (EMT), migration, and proliferation. 1 Cell-cell contacts in RPE consist of gap-junctions, 4 adherens junctions (AJs), 5 and tight junctions. 1 Gap junctions are composed of two hemichannels that allow the rapid transport of small ions and compounds.…”

mentioning

confidence: 99%

“…Of all currently identified connexin genes, connexin 43 is the most extensively expressed and has been investigated in the most detail. [6][7][8] Connexin 43 observed in RPE 4,9 is capable of mediating intercellular dye transfer 4 and protecting against oxidative stress-induced cell death. 9 Zona occludens 1 (ZO-1) was one of the first recognized and best-studied tight junction proteins.…”

mentioning

confidence: 99%

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The Interplay Between E-Cadherin, Connexin 43, and Zona Occludens 1 in Retinal Pigment Epithelial Cells

Bao

Yang

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Cell-cell contact in retinal pigment epithelium (RPE) involves adherent junctions, gap junctions, and tight junctions, which are primarily composed by E-cadherin, zona occludens 1 (ZO-1), and connexin 43, respectively. Here, we aimed to explore the relationship and interplay between these junction-associated proteins. METHODS. E-cadherin, connexin 43, and ZO-1 expression in human primary RPE in the early phase after TGF-b1 stimulation was detected. The knockdown of E-cadherin, ZO-1, and connexin 43 was performed to characterize the regulatory network involving these three proteins. Dye transfer and FITC-dextran permeability assays were conducted to observe the epithelial functional alterations. Transmission electron microscopy (TEM) was used to observe the ultrastructure of the cell-cell junctions in mouse RPE. The immunofluorescence staining and coimmunoprecipitation were performed to observe the colocalization and the physical association of E-cadherin, ZO-1, and connexin 43. RESULTS. Among these three components, E-cadherin appeared to be the first protein that was downregulated after TGF-b1 treatment. The ultrastructures of adherent junctions, gap junctions, and tight junctions could be observed in mouse RPE by TEM. E-cadherin, ZO-1, and connexin 43 were colocalized and physically bound to each other. The knockdown of one of these three proteins led to downregulation of the other two proteins and compromised epithelial function. CONCLUSIONS. E-cadherin, ZO-1, and connexin 43 were physically associated with each other and were mutually regulated. To enhance the understanding of cell-cell contacts, a holistic view is needed. Our results provide new insights in RPE disorders such as proliferative vitreoretinopathy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Interplay Between E-Cadherin, Connexin 43, and Zona Occludens 1 in Retinal Pigment Epithelial Cells

Bao

Yang

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…1) Chemical synthesis of a photoreactive DHA analogue was performed according to the previously reported method, using DHA in place of palmitic acid. 26) In brief, a phenylalanine analogue was used to introduce a diazirine photophore at the carboxyl terminus of DHA as shown in Supplementary Mate-…”

Section: Methodsmentioning

confidence: 99%

Multiple Cellular Transport and Binding Processes of Unesterified Docosahexaenoic Acid in Outer Blood–Retinal Barrier Retinal Pigment Epithelial Cells

Tachikawa

Akanuma

Imai

et al. 2018

Biological & Pharmaceutical Bulletin

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Docosahexaenoic acid (DHA, 22 : 6) is an essential omega-3 long-chain polyunsaturated fatty acid that plays a pivotal role in vision. The purpose of this study was to clarify the cellular uptake and binding processes of free and protein-bound unesterified DHA in retinal pigment epithelial cell (RPE) line ARPE-19 as a model of the human outer blood-retinal barrier and isolated porcine RPE cell fractions. Uptake of free [C]DHA by ARPE-19 cells was saturable with a Michaelis-Menten constant of 283 µM, and was significantly inhibited by eicosapentaenoic acid, arachidonic acid, and linoleic acid, but not by oleic acid. Further, the uptakes of [C]DHA associated with retinol-binding protein ([C]DHA-RBP), [C]DHA associated with low-density lipoprotein ([C]DHA-LDL) and [C]DHA associated with bovine serum albumin ([C]DHA-BSA) in ARPE-19 cells increased time-dependently at 37°C, and were significantly reduced at 4°C, suggesting the involvement of energy-dependent transport processes. [C]DHA-LDL uptake by ARPE-19 cells was significantly inhibited by excess unlabeled LDL, but not by an inhibitor of scavenger receptor B type I. Fatty acid transport protein (FATP) 2 and 4 mRNAs were expressed in ARPE-19 cells, and [C]DHA uptake was observed in FATP2- and FATP4-expressing Xenopus oocytes. Photo-reactive crosslinking and mass spectrometry analyses identified 65-kDa retinal pigment epithelium-specific protein (RPE65) as a DHA-binding protein in porcine RPE cell membrane fractions. Thus, RPE cells possess multiple cellular transport/binding processes for unesterified DHA, involving at least partly FATP2, FATP4, LDL, RBP, and RPE65.

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Effects of electroacupuncture at Neiguan (PC6) on arrhythmia during myocardial infarction in a rat model of myocardial ischemia-reperfusion

Xia

et al. 2023

J. Acupunct. Tuina. Sci.

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Expression and function of connexin 43 protein in mouse and human retinal pigment epithelial cells as hemichannels and gap junction proteins

Cited by 15 publications

References 45 publications

The Interplay Between E-Cadherin, Connexin 43, and Zona Occludens 1 in Retinal Pigment Epithelial Cells

The Interplay Between E-Cadherin, Connexin 43, and Zona Occludens 1 in Retinal Pigment Epithelial Cells

Multiple Cellular Transport and Binding Processes of Unesterified Docosahexaenoic Acid in Outer Blood–Retinal Barrier Retinal Pigment Epithelial Cells

Effects of electroacupuncture at Neiguan (PC6) on arrhythmia during myocardial infarction in a rat model of myocardial ischemia-reperfusion

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