Role of FSH and triiodothyronine in Sertoli cell development expressed by formation of connexin 43-based gap junctions

2011 ◽  
Vol 315A (6) ◽  
pp. 329-336 ◽  
Author(s):  
Katarzyna Marchlewska ◽  
Krzysztof Kula ◽  
Renata Walczak-Jedrzejowska ◽  
Elzbieta Oszukowska ◽  
Eliza Filipiak ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Sertoli Cell ◽  
Connexin 43 ◽  
Cell Development

CX43 expression, phosphorylation, and distribution in the normal and autoimmune orchitic testis with a look at gap junctions joining germ cell to germ cell

2011 ◽  
Vol 300 (1) ◽  
pp. R121-R139 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Casimir D. Akpovi ◽  
Li Chen ◽  
Robert Day ◽  
María L. Vitale
Keyword(s):  
Cell Differentiation ◽  
Gap Junctions ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Connexin 43 ◽  
Cx43 Expression ◽  
Cx43 Protein ◽  
Cx43 Mrna

Spermatogenesis requires connexin 43 (Cx43).This study examines normal gene transcription, translation, and phosphorylation of Cx43 to define its role on germ cell growth and Sertoli cell's differentiation, and identifies abnormalities arising from spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and a natural model for autoimmunity. Northern blot analysis detected 2.8- and a 3.7-kb Cx43 mRNA bands in seminiferous tubule-enriched fractions. Cx43 mRNA increased in seminiferous tubule-enriched fractions throughout development and then seasonally with the completion of spermatogenesis. Cx43 protein levels increased transiently during the colonization of the tubules by the early-stage spermatocytes. Cx43 phosphorylated (PCx43) and nonphosphorylated (NPCx43) in Ser368 decreased during the periods of completion of meiosis and Sertoli cell differentiation, while Cx43 mRNA remained elevated throughout. PCx43 labeled chiefly the plasma membrane except by stage VII when vesicles were also labeled in Sertoli cells. Vesicles and lysosomes in Sertoli cells and the Golgi apparatus in the round spermatids were NPCx43 positive. A decrease in Cx43 gene expression was matched by a Cx43 protein increase in the early, not the late, phase of AIO. Total Cx43 and PCx43 decreased with the advance of orchitis. The study makes a novel finding of gap junctions connecting germ cells. The data indicate that Cx43 protein expression and phosphorylation in Ser368 are stage-specific events that may locally influence the acquisition of meiotic competence and the Sertoli cell differentiation in normal testis. AIO modifies Cx43 levels, suggesting changes in Cx43-mediated intercommunication and spermatogenic activity in response to cytokines imbalances in Sertoli cells.

CONDITIONAL KNOCKOUT OF CONNEXIN 43 IN MOUSE UTERUS UNCOVERS AN ESSENTIAL ROLE OF GAP JUNCTIONS DURING PREGNANCY

2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 205-205
Author(s):  
Mary Laws ◽  
Francesco DeMayo ◽  
John Lydon ◽  
Milan Bagchi ◽  
Indrani Bagchi
Keyword(s):  
Gap Junctions ◽  
Connexin 43 ◽  
Essential Role ◽  
Conditional Knockout ◽  
Mouse Uterus

scholarly journals Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Harissios Vliagoftis ◽  
Cory Ebeling ◽  
Ramses Ilarraza ◽  
Salahaddin Mahmudi-Azer ◽  
Melanie Abel ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Gap Junction ◽  
Peripheral Blood ◽  
Connexin 43 ◽  
Transendothelial Migration ◽  
Glycyrrhetinic Acid ◽  
Dependent Manner ◽  
Dye Transfer ◽  
Blood Eosinophils

Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

Role of connexin 43 in different forms of intercellular communication – gap junctions, extracellular vesicles and tunnelling nanotubes

2017 ◽  
Vol 130 (21) ◽  
pp. 3619-3630 ◽  
Author(s):  
Teresa M. Ribeiro-Rodrigues ◽  
Tânia Martins-Marques ◽  
Sandrine Morel ◽  
Brenda R. Kwak ◽  
Henrique Girão
Keyword(s):  
Gap Junctions ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Connexin 43 ◽  
Communication Gap

scholarly journals TAMI-36. CONNEXIN 43 BLOCKADE INHIBITS PROLIFERATION IN IDH1-MUTANT GLIOMA CELLS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii220-ii221
Author(s):  
Lisa Melamed ◽  
Christine Lee ◽  
Hiroaki Nagashima ◽  
Julie Miller ◽  
Hiroaki Wakimoto ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Tumor Cells ◽  
Connexin 43 ◽  
Therapeutic Window ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Carboxyl Terminal ◽  
Cell Networks ◽  
Nad Depletion ◽  
Dependent Mechanism

Abstract IDH1-mutant gliomas are characteristically sensitive to NAD+ depletion. It is known that NAD+ can move between cells through gap junctions, which provides an opportunity for treatments that prevent NAD+ sharing across tumor cells, effectively decreasing available NAD+. Previous studies have also shown the role of connexin 43 (Cx43) in mediating communication in glioma cell networks and have identified Cx43 as a potential mediator of temozolomide resistance in glioma. We hypothesized that blocking Cx43 would prevent intercellular NAD+ sharing in IDH-mutant gliomas, causing tumor cells to be more vulnerable to metabolic NAD+ depletion via nicotinamide phosphoribosyltransferase (NAMPT) inhibitors and temozolomide (TMZ) treatment. Here, we show that blockade of Cx43 with α-connexin carboxyl-terminal (ACT1) is able to inhibit growth of patient-derived IDH1-mutant tumor cells. ACT1 sensitizes cells to TMZ and inhibits growth of IDH1-mutant gliomas via an NAD-dependent mechanism. We also found that ACT1 can be used in combination with other NAD-depleting drugs, such as NAMPT inhibitors, to enhance its effect and provide a viable therapeutic window. Overall, our results suggest that ACT1 may enhance the efficacy of treatments for IDH1-mutant tumors by blocking metabolic buffering through tumor cell gap junctions.

scholarly journals The Molecular Mechanism of Sex Hormones on Sertoli Cell Development and Proliferation

2021 ◽  
Vol 12 ◽  
Author(s):  
Wasim Shah ◽  
Ranjha Khan ◽  
Basit Shah ◽  
Asad Khan ◽  
Sobia Dil ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Sex Hormones ◽  
Sertoli Cells ◽  
Production Capacity ◽  
Cell Development ◽  
Seminiferous Tubules ◽  
Recent Advancement ◽  
Specific Number

Sustaining and maintaining the intricate process of spermatogenesis is liable upon hormones and growth factors acting through endocrine and paracrine pathways. The Sertoli cells (SCs) are the major somatic cells present in the seminiferous tubules and are considered to be the main regulators of spermatogenesis. As each Sertoli cell supports a specific number of germ cells, thus, the final number of Sertoli cells determines the sperm production capacity. Similarly, sex hormones are also major regulators of spermatogenesis and they can determine the proliferation of Sertoli cells. In the present review, we have critically and comprehensively discussed the role of sex hormones and some other factors that are involved in Sertoli cell proliferation, differentiation and maturation. Furthermore, we have also presented a model of Sertoli cell development based upon the recent advancement in the field of reproduction. Hence, our review article provides a general overview regarding the sex hormonal pathways governing Sertoli cell proliferation and development.

scholarly journals Small Interference RNA Targeting Connexin-43 Improves Motor Function and Limits Astrogliosis After Juvenile Traumatic Brain Injury

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141984709 ◽  
Author(s):  
Aleksandra Ichkova ◽  
Andrew M. Fukuda ◽  
Nina Nishiyama ◽  
Germaine Paris ◽  
Andre Obenaus ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gap Junctions ◽  
Motor Function ◽  
Connexin 43 ◽  
Post Injury ◽  
Edema Formation ◽  
Small Interference Rna ◽  
Interference Rna

Juvenile traumatic brain injury (jTBI) is the leading cause of death and disability for children and adolescents worldwide, but there are no pharmacological treatments available. Aquaporin 4 (AQP4), an astrocytic perivascular protein, is increased after jTBI, and inhibition of its expression with small interference RNA mitigates edema formation and reduces the number of reactive astrocytes after jTBI. Due to the physical proximity of AQP4 and gap junctions, coregulation of AQP4 and connexin 43 (Cx43) expressions, and the possibility of water diffusion via gap junctions, we decided to address the potential role of astrocytic gap junctions in jTBI pathophysiology. We evaluated the role of Cx43 in the spread of the secondary injuries via the astrocyte network, such as edema formation associated with blood–brain barrier dysfunctions, astrogliosis, and behavioral outcome. We observed that Cx43 was altered after jTBI with increased expression in the perilesional cortex and in the hippocampus at several days post injury. In a second set of experiments, cortical injection of small interference RNA against Cx43 decreased Cx43 protein expression, improved motor function recovery, and decreased astrogliosis but did not result in differences in edema formation as measured via T2-weighted imaging or diffusion-weighted imaging at 1 day or 3 days. Based on our findings, we can speculate that while decreasing Cx43 has beneficial roles, it likely does not contribute to the spread of edema early after jTBI.

Effect of oestradiol and progesterone on the instant and directional velocity of microsphere movements in the rat oviduct: gap junctions mediate the kinetic effect of oestradiol

2007 ◽  
Vol 19 (5) ◽  
pp. 634 ◽  
Author(s):  
Mariana Ríos ◽  
Marcela Hermoso ◽  
Trinidad M. Sánchez ◽  
Horacio B. Croxatto ◽  
Manuel J. Villalón
Keyword(s):  
Gap Junctions ◽  
Connexin 43 ◽  
Single Injection ◽  
Control Group ◽  
Mrna Levels ◽  
Kinetic Effect ◽  
Egg Transport ◽  
Opposing Effects ◽  
Cx 43

The oviducal transport of eggs to the uterus normally takes 72–96 h in the rat, but this is reduced to less than 20 h after a single injection of oestradiol (E2). This accelerated transport is associated with an increased frequency of pendular movements in the isthmic segment of the oviduct, with increased levels of the gap junction (GJ) component Connexin (Cx) 43, and is antagonised by progesterone (P). In the present study, we investigated the effect of these hormones on the instant and directional velocity of pendular movements and the role of the GJ and its Cx43 component in the kinetic response of the oviduct to E2 and P. Using microspheres as egg surrogates, microsphere instant velocity (MIV) was measured following treatment with E2, P or P + E2, which accelerate or delay egg transport. Microspheres were delivered into the oviduct of rats on Day 1 of pregnancy and their movement within the isthmic segment was recorded. Oestrogen increased MIV with faster movement towards the uterus. After P or P + E2, MIV was similar to that in the control group. Two GJ uncouplers, namely 18α- and 18β-glycyrrhetinic acid, blocked the effect of E2 on MIV. Connexin 43 mRNA levels increased over that seen in control with all treatments. In conclusion, the effects of E2 on MIV resulted in faster movements that produced accelerated egg transport towards the uterus. Gap junctions are probably involved as smooth muscle synchronisers in this kinetic effect of E2, but the opposing effects of E2 and P are not exerted at the level of Cx43 transcription.

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