Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant inherited disease caused by mutations of the human gap junction alpha 1 gene, which encodes the protein Connexin-43. Patients with ODDD may present with neurological deficits with a typical pleiotropic combination of characteristic craniofacial, ophthalmological, phalangeal, and dental anomalies. In this report, we describe the first genetically confirmed Korean ODDD patient, who presented with spastic paraparesis. We will also review the neurological aspects of ODDD as reported in the literature.
Gap Junctions ; Humans ; Muscle Spasticity* ; Paraparesis, Spastic*

The aim of this study was to evaluate the histopathologic changes of the pigmented rabbit ratina after endocryopexy. We investigated the differences or similarity among endocryopexy, transscleral cryopexy and laser phocoagulation. Their ultrastructural changes were observed with light and electron microscope. The results were as follows; 1. The first day after endocryopexy, we observed rupture of the internal limiting membrane, breakdown the inner and outer retina, separation of intercellular gap junction of pigment epithelial cells, and accumulation of exudation within subretinal space. 2. In the 8th days, there are mull iplication of retinal pigment epithelial cell layer and development of basal infolding. 3. The present study suggested that effects of endocryopexy on the retina to cause chorioretinal adhesion was similar to transscleral cryopexy or laser photocoagulation However it should be operated on the premise that in requires technical skill for the purpose of clinical application.
Epithelial Cells ; Gap Junctions ; Light Coagulation ; Membranes ; Retina* ; Retinaldehyde ; Rupture

Horizontal cells (HCs) of the mammalian retina are interneurons that provide negative feedback to photoreceptors in the outer plexiform layer (OPL) where the first synapse occurs and contribute to the center surround antagonism that underlies the receptive field properties of many retinal neurons. These functions of HCs are thought to be attributed to their coupled network via gap junctions. Two kinds of connexin (Cx) proteins, Cx50 and 57 are known to form gap junctions of HCs. However, little is known about precise localization of gap junctions within HCs. Thus, this study was designed to determine the localization of HC gap junctions at subcellular level. In vertical ultrathin sections of the rabbit retina, gap junctions composed of Cx50 and 57 were identified in the OPL by the electron-dense reaction products. Each Cx50 and 57 gap junction on putative HC processes showed its own distinct features. Cx50 gap junction was bigger in size and localized more proximally than Cx57. In addition, Cx57 gap junctions had distinct shape. That is, about a half of them appeared to be invaginated or endocytosed in shape. The differences in shape, size and subcellular localization between Cx50 and 57 gap junctions may provide the insights into the function of different types of horizontal cell.
Gap Junctions ; Interneurons ; Proteins ; Retina ; Retinal Neurons ; Synapses

Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ) channels. Cx46 and Cx50 are also known to function as conductive hemichannels. As part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors were used to examine their effect on Cx46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, 1 microM) reversibly reduced outward hemichannel currents up to ~28% (n=4). However, overall shapes of Cx46 hemichannel current traces (outward and inward currents) were not changed by these drugs. These results suggest that BPA and OP are likely to occupy the pore of Cx46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.
Connexins ; Endocrine Disruptors ; Gap Junctions ; Membrane Proteins ; Oocytes ; Xenopus

The contractility of corporal smooth muscle plays a critical role in human penile erectile process. Understanding the initiation, maintenance and modulation of corporal smooth muscle tone is a prequisite to improve understanding, diagnosis and treatment of erectile dysfunction. Despite this fact, indentification of both the precise mechanistic basis by which various agents exert their effects on individual corporal smooth muscle cells, moreover, the process by which these signals are spread among the diverse array of parenchymal cells in the paired corporal, remain somewhat of a physiological enigma. Therefore, this article aims at: 1. to review current knowledge of the regulation of corporal smooth muscle tone at the cellular and molecular level; 2. to review various methods used in the study of gap junction channel.
Animals ; Connexins ; physiology ; Gap Junctions ; physiology ; Humans ; Intercellular Junctions ; physiology ; Male ; Muscle, Smooth ; physiology ; Penis ; cytology

OBJECTIVETo investigate the effects of inhibiting gap junctional intercellular communication on hypoxia/reoxygenation injury in astrocytes.

METHODSPrimary cultured cerebral cortical astrocytes of neonate rats were divided into normal control group, hypoxia reoxygenation injury group and 18-α-glycyrrhetinic acid and oleamide (gap junctional intercellular channel inhibitors) group. The gap junction intercellular communication was determined by Parachute assay. The viability of astrocyes was detected by MTT assay. The apoptosis of astrocytes were detected with annexin V/PI and Hoechst 33258 staining.

RESULTSCompared with the normal control group, the gap junctional function of astrocytes was increased significantly in ischemia/reperfusion group (P<0.01), the surviving fraction of astrocytes decreased significantly (P<0.01) and its cell apoptosis ratio increased significantly (P<0.01). Compared with the ischemia/reperfusion group, the gap junctional function of astrocytes in18-α-glycyrrhetinic acid and oleamide group decreased significantly (P<0.01), the viability of astrocytes increased significantly (P<0.01), while cell apoptosis decreased significantly (P<0.01).

CONCLUSIONInhibition of intercellular gap junction has protective effect against hypoxia/reoxygenation injury in astrocytes.

Animals ; Apoptosis ; Astrocytes ; cytology ; pathology ; Cell Communication ; Cell Hypoxia ; Cells, Cultured ; Gap Junctions ; Oxygen ; Rats

OBJECTIVETo probe into expression of connexin 43 (Cx43) in the meridians of the normal healthy rats and the relation among connexin, gap junction and meridian.

METHODSPowerVision two step immunohistochemical technique and ASIAS-2000 automatical image-scan analyzing system were used to detect Cx43 level and distribution in the Kidney and Bladder Meridians of the rat.

RESULTSCx43 expressed mainly in skin epithelia, fibroblasts and mast cells of the subcutaneous layer. And expression of Cx43 in the Kidney and Bladder Meridians was significantly more than that in the control lines (P < 0.01).

CONCLUSIONConnexins and gap junctions have close relation with the meridians, and the gap junctional intercellular communication may play an important role in the function of meridians.

Animals ; Cell Communication ; Connexin 43 ; metabolism ; Connexins ; Gap Junctions ; metabolism ; Meridians ; Rats

Erythrokeratodermia variabilis is an autosomal-dominant inherited disease associated with a mutation in gap junction beta (GJB) 3 and 4. It shows two characteristic features: migratory and irregularly shaped erythematous lesions usually accompanied by a burning sensation and fixed, symmetrically located hyperkeratotic plaques. A 6-year-old boy had developed erythematous scaly patches with a geographic pattern on the entire body at age 1, and the lesions had migrated with an irregular pattern. Accompanying hyperkeratotic plaque developed on the trunk and both legs when he was 4 years old. As he grew older, the erythematous patches progressively disappeared and the hyperkeratotic plaque dominantly remained. His family history was unidentifiable because he was adopted at birth. Pathologic findings showed hyperkeratosis and superficial perivascular inflammation. Based on the clinical and pathologic features, we diagnosed erythrokeratodermia variabilis in this patient. Herein, we report a case of erythrokeratodermia variabilis showing gradual disappearance of erythema.
Burns ; Child ; Erythema* ; Erythrokeratodermia Variabilis* ; Gap Junctions ; Humans ; Inflammation ; Leg ; Male ; Parturition ; Sensation

PURPOSE: Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. METHODS: To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. RESULTS: A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. CONCLUSION: We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.
Animals ; Antibodies, Monoclonal ; Bystander Effect* ; Connexin 43 ; Gap Junctions ; Genetic Therapy* ; Immunohistochemistry ; Mice ; Neuroblastoma* ; Simplexvirus ; Thymidine

PURPOSE: Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC. METHODS: NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared. RESULTS: Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect. CONCLUSION: These results indicated that the increase of GJIC using Cx37 have potentiated the by stander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.
Bystander Effect* ; Calcium ; Gap Junctions* ; Genes, Neoplasm ; Genetic Therapy* ; Herpes Simplex ; Thymidine