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Robert D Johnson, Patrizia Camelliti
The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes...
March 15, 2018: International Journal of Molecular Sciences
Shivani Mishra, Himani Pandey, Priyanka Srivastava, Kausik Mandal, Shubha R Phadke
OBJECTIVE: To determine the prevalence and spectrum of Connexin 26 (GJB2) mutations in pre-lingual non-syndromic hearing loss (NSHL) patients in authors' centre and to review the data of Indian patients from the literature. METHODS: Sanger sequencing of entire coding region contained in single exon (Exon 2) of GJB2 gene in 15 patients of NSHL. RESULTS: GJB2 mutations were found in 40% (6/15) of NSHL patients, out of which mono-allelic were 33...
March 15, 2018: Indian Journal of Pediatrics
F de Michele, J Poels, M G Giudice, F De Smedt, J Ambroise, M Vermeulen, D Gruson, C Wyns
STUDY QUESTION: How does the formation of the blood-testis barrier (BTB), as reflected by the expression of connexin 43 and claudin 11 proteins during the pubertal transition period, take place in vitro compared to samples from a large cohort of pre/peripubertal boys? SUMMARY ANSWER: The BTB connexin 43 and claudin 11 expression patterns appeared to be partially achieved in organotypic culture when compared to that in samples from 71 pre/peripubertal patients. WHAT IS KNOWN ALREADY: Although alterations in the protein expression patterns of the BTB, whose main components are connexin 43 and claudin 11, are known to be associated with impaired spermatogenesis in mice and adult men, there is a lack of knowledge on its formation in pre-peripubertal human tissue both in vitro and in vivo...
March 12, 2018: Molecular Human Reproduction
Jan Raska, Lucie Ctverackova, Aneta Dydowiczova, Iva Sovadinova, Ludek Blaha, Pavel Babica
HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, α-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed...
March 10, 2018: Toxicology and Applied Pharmacology
Sara Crespo Yanguas, Tereza C da Silva, Isabel V A Pereira, Joost Willebrords, Michaël Maes, Marina Sayuri Nogueira, Inar Alves de Castro, Isabelle Leclercq, Guilherme R Romualdo, Luís F Barbisan, Luc Leybaert, Bruno Cogliati, Mathieu Vinken
Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation...
March 12, 2018: International Journal of Molecular Sciences
Akiyuki Taruno
Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels...
March 11, 2018: International Journal of Molecular Sciences
Annalucia Carbone, Roberto Zefferino, Elisa Beccia, Valeria Casavola, Stefano Castellani, Sante Di Gioia, Valentina Giannone, Manuela Seia, Antonella Angiolillo, Carla Colombo, Maria Favia, Massimo Conese
We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs...
2018: Stem Cells International
Ipsita Mohanty, Subas Chandra Parija, Sujit Suklabaidya, Satish Rattan
Extracellular pH is an important physiological determinant of vascular tone that is normally maintained within 7.35-7.45. Any change outside this range leads to severe pathological repercussions. We investigated the unknown effects of extracellular acidosis on relaxation in the superior mesenteric artery (SMA) of goat. SMA rings were employed to maintain isometric contractions at extracellular pH (pHo ) 7.4 and 6.8. We analyzed the effect of acidosis (pHo 6.8) compared to physiological pH (pHo 7.4) on three signaling mediators of endothelium-dependent hyperpolarization: nitric oxide (NO), prostaglandin I2 (PGI2 ), and myoendothelial gap junctions (MEGJ)...
March 7, 2018: European Journal of Pharmacology
Sarah Falk
Pain is a major complication for cancer patients significantly compromising their quality of life. Current treatment is far from optimal and particularly bone-related cancer pain poses an increasing clinical and socio-economical problem. Connexins, key proteins in cell-cell communication, have the potential to affect cancer-induced bone pain at multiple levels, including nociceptive signaling and bone degradation. This study tested the analgesic potential of carbenoxolone, a broad-acting connexin blocker, in a mouse model of cancer-induced bone pain...
March 6, 2018: Pain
Amandine Jullienne, Andrew M Fukuda, Aleksandra Ichkova, Nina Nishiyama, Justine Aussudre, André Obenaus, Jérôme Badaut
Aquaporins (AQPs) facilitate water diffusion through the plasma membrane. Brain aquaporin-4 (AQP4) is present in astrocytes and has critical roles in normal and disease physiology. We previously showed that a 24.9% decrease in AQP4 expression after in vivo silencing resulted in a 45.8% decrease in tissue water mobility as interpreted from magnetic resonance imaging apparent diffusion coefficients (ADC). Similar to previous in vitro studies we show decreased expression of the gap junction protein connexin 43 (Cx43) in vivo after intracortical injection of siAQP4 in the rat...
March 8, 2018: Scientific Reports
Cong-Yuan Xia, Zhen-Zhen Wang, Tohru Yamakuni, Nai-Hong Chen
Major depressive disorder (MDD) is a chronic and debilitating illness that affects over 350 million people worldwide; however, current treatments have failed to cure or prevent the progress of depression. Increasing evidence suggests a crucial role for connexins in MDD. In this review, we have summarised recent accomplishments regarding the role of connexins, gap junctions, and hemichannels in the aetiology of MDD, and discussed the limitations of current research. A blockage of gap junctions or hemichannels induces depressive behaviour...
March 5, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Michela Pecoraro, Michele Ciccarelli, Antonella Fiordelisi, Guido Iaccarino, Aldo Pinto, Ada Popolo
Doxorubicin (DOXO) administration induces alterations in Connexin 43 (Cx43) expression and localization, thus, inducing alterations in chemical and electrical signal transmission between cardiomyocytes and in intracellular calcium homeostasis even evident after a single administration. This study was designed to evaluate if Diazoxide (DZX), a specific opener of mitochondrial KATP channels widely used for its cardioprotective effects, can fight DOXO-induced cardiotoxicity in a short-time mouse model. DZX (20 mg/kg i...
March 7, 2018: International Journal of Molecular Sciences
François Cossais, Sebastian Leuschner, Martina Barrenschee, Christina Lange, Michael Ebsen, Ilka Vogel, Martina Böttner, Thilo Wedel
BACKGROUND: Diverticular disease (DD) is a common gastrointestinal inflammatory disorder associated with an enteric neuropathy. Although enteric glial cells (EGCs) are essential regulators of intestinal inflammation and motility functions, their contribution to the pathophysiology of DD remains unclear. Therefore, we analyzed the expression of specific EGC markers in patients with DD. MATERIALS AND METHODS: Expression of the glial markers S100β, GFAP, Sox10, and Connexin 43 was analyzed by real-time quantitative PCR in colonic specimens of patients with DD and in that of controls...
March 6, 2018: Journal of Clinical Gastroenterology
Jian-Qiang Huang, Xiao-Yang Chen, Fang Huang, Ji-Min Fan, Xiao-Wei Shi, Yan-Kai Ju
Connexion 43 (Cx43), a gap junction protein, is expressed abundantly in the airway and has been implicated in the pathogenesis of asthma. However, the effects of blocking Cx43 in asthma remain unclear. We investigated the therapeutic effects of two specific Cx43 inhibitors (Gap26 and Gap27) on the development of allergic airway disease in mice. Allergic asthma was induced in BALB/c mice by sensitization and challenge with ovalbumin (OVA). Different doses of Cx43 inhibitors were administered by aerosol inhalation 1 h after OVA challenge on days 21 and 23...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Jing Li, Shuai Wang, Jie Bai, Xiao-Lei Yang, Yun-Long Zhang, Yi-Lin Che, Hui-Hua Li, Yan-Zong Yang
Angiotensin II (Ang II) and inflammation are associated with pathogenesis of atrial fibrillation (AF), but the underlying molecular mechanisms of these events remain unknown. The immunoproteasome has emerged as a critical regulator of inflammatory responses. Here, we investigated its role in Ang II-induced AF in immunosubunit PSMB10 (also known as β2i or LMP10) knockout (KO) mice. AF was induced by Ang II infusion (2000 ng/min per kg). PSMB10 expression and trypsin-like activity were increased in atrial tissues and serum from Ang II-treated mice or serum from patients with AF...
March 5, 2018: Hypertension
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Anuttoma Ray is the first author on 'Dileucine-like motifs in the C-terminal tail of connexin32 control its endocytosis and assembly into gap junctions', published in Journal of Cell Science. Anuttoma is a PhD student in the lab of Dr Parmender P. Mehta at the University of Nebraska Medical Center, Omaha, USA, investigating the molecular mechanisms that regulate assembly of connexins into gap junctions...
March 2, 2018: Journal of Cell Science
Mélanie Busby, Michael T Hallett, Isabelle Plante
Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes...
February 28, 2018: International Journal of Molecular Sciences
Runhong Lei, Xue Bai, Yanan Chang, Juan Li, Yanxia Qin, Kui Chen, Weihong Gu, Shibo Xia, Jiaxin Zhang, Zhenbo Wang, Gengmei Xing
The excellent biocompatibility and biological effects of fullerenol and its derivatives make their biomedical application promising. The potential effects of fullerenol in mammals have been extensively studied, but little is known about its effects on female reproduction. Using canonical oocyte-granulosa cell complexes (OGCs) in vitro maturation culture model, we investigated the effect of fullerenol on the first oocyte meiotic resumption. In the surrounding granulosa cells, fullerenol nanoparticles occluded the extracellular domain of the epidermal growth factor receptor (EGFR) to reduce EGFR-ligand binding and subsequent extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation, which involved the regulation of connexin 43 (CX43) expression and internalization...
March 1, 2018: International Journal of Molecular Sciences
Niklas Meyer, Nadine Richter, Zoya Fan, Gabrielle Siemonsmeier, Tatyana Pivneva, Philipp Jordan, Christian Steinhäuser, Marcus Semtner, Christiane Nolte, Helmut Kettenmann
In the optic nerve, oligodendrocytes maintain axonal function by supplying lactate as an energy substrate. Here, we report that, in acute brain slices of the mouse corpus callosum, exogenous glucose deprivation (EGD) abolished compound action potentials (CAPs), which neither lactate nor pyruvate could prevent. Loading an oligodendrocyte with 20 mM glucose using a patch pipette prevented EGD-mediated CAP reduction in about 70% of experiments. Loading oligodendrocytes with lactate rescued CAPs less efficiently than glucose...
February 27, 2018: Cell Reports
Wen Shi, Manuel A Riquelme, Sumin Gu, Jean X Jiang
Elevated oxidized stress contributes to lens cataracts and gap junctions play important roles in maintaining lens transparency. Besides gap junctions, connexins form hemichannels. Here, we report a new mechanism of hemichannels that mediate transport of reductant glutathione into lens fiber cells and protect cells against oxidative stress. Hemichannels were opened in response to H2 O2 in lens fiber cells and were inhibited by two dominant negative mutants of Cx50; Cx50P88S that inhibits both gap junctions and hemichannels and Cx50H156N that only inhibits hemichannels, but not gap junctions...
February 27, 2018: Journal of Cell Science
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