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https://www.readbyqxmd.com/read/29228446/telmisartan-reduces-arrhythmias-through-increasing-cardiac-connexin43-by-inhibiting-il-17-after-myocardial-infarction-in-rats
#1
H-Y Chang, X Li, Y Tian
OBJECTIVE: To observe the expressions of myocardial connexin43 (Cx43) and interleukin-17 (IL-17) in acute myocardial infarction (AMI) rats and investigate its possible mechanism of telmisartan in the prevention and treatment of arrhythmia in AMI. MATERIALS AND METHODS: Sprague Dawley (SD) rats were selected and myocardial infarction model was established. After the successful modeling, the rats were randomly divided into three groups: Sham group, MI group, Telm group...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29223529/corticosterone-impairs-gap-junctions-in-the-prefrontal-cortical-and-hippocampal-astrocytes-via-different-mechanisms
#2
Cong-Yuan Xia, Zhen-Zhen Wang, Zhao Zhang, Jiao Chen, Ying-Ying Wang, Yu-Xia Lou, Yan Gao, Piao Luo, Qian Ren, Guo-Hua Du, Nai-Hong Chen
Increasing evidence has implicated astrocyte pathology in the etiopathology of major depressive disorder (MDD). In particular, dysfunction of gap junctions in astrocytes is a potential target for MDD treatment. However, the mechanism underlying stress-induced dysfunction of gap junctions is still unknown. We therefore studied the mechanism of stress-induced dysfunction of gap junctions in prefrontal cortical and hippocampal astrocytes. Corticosterone (CORT) was used to induce stress conditions; CORT damaged the function of gap junctions, which resulted from less distribution of connexin43 (Cx43) on membranes and the enhanced phosphorylation of Cx43 at S368...
December 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29200997/connexin43-hemichannels-in-satellite-glial-cells-can-they-influence-sensory-neuron-activity
#3
REVIEW
Mauricio A Retamal, Manuel A Riquelme, Jimmy Stehberg, Julio Alcayaga
In this review article, we summarize the current insight on the role of Connexin- and Pannexin-based channels as modulators of sensory neurons. The somas of sensory neurons are located in sensory ganglia (i.e., trigeminal and nodose ganglia). It is well known that within sensory ganglia, sensory neurons do not form neither electrical nor chemical synapses. One of the reasons for this is that each soma is surrounded by glial cells, known as satellite glial cells (SGCs). Recent evidence shows that connexin43 (Cx43) hemichannels and probably pannexons located at SGCs have an important role in paracrine communication between glial cells and sensory neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29186067/immunohistochemical-characterization-of-connexin43-expression-in-a-mouse-model-of-diabetic-retinopathy-and-in-human-donor-retinas
#4
Odunayo O Mugisho, Colin R Green, Jie Zhang, Nicolette Binz, Monica L Acosta, Elizabeth Rakoczy, Ilva D Rupenthal
Diabetic retinopathy (DR) develops due to hyperglycemia and inflammation-induced vascular disruptions in the retina with connexin43 expression patterns in the disease still debated. Here, the effects of hyperglycemia and inflammation on connexin43 expression in vitro in a mouse model of DR and in human donor tissues were evaluated. Primary human retinal microvascular endothelial cells (hRMECs) were exposed to high glucose (HG; 25 mM) or pro-inflammatory cytokines IL-1β and TNF-α (10 ng/mL each) or both before assessing connexin43 expression...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29183963/distinct-moieties-underlie-biphasic-h-gating-of-connexin43-channels-producing-a-ph-optimum-for-intercellular-communication
#5
Carolina D Garciarena, Akif Malik, Pawel Swietach, Alonso P Moreno, Richard D Vaughan-Jones
Most mammalian cells can intercommunicate via connexin-assembled, gap-junctional channels. To regulate signal transmission, connexin (Cx) channel permeability must respond dynamically to physiological and pathophysiological stimuli. One key stimulus is intracellular pH (pHi), which is modulated by a tissue's metabolic and perfusion status. Our understanding of the molecular mechanism of H+ gating of Cx43 channels-the major isoform in the heart and brain-is incomplete. To interrogate the effects of acidic and alkaline pHi on Cx43 channels, we combined voltage-clamp electrophysiology with pHi imaging and photolytic H+ uncaging, performed over a range of pHi values...
November 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29179619/urban-fine-particulate-matter-pm2-5-exposure-destroys-blood-testis-barrier-btb-integrity-through-excessive-ros-mediated-autophagy
#6
Yi Wei, Xi-Ning Cao, Xiang-Liang Tang, Lian-Ju Shen, Tao Lin, Da-Wei He, Sheng-de Wu, Guang-Hui Wei
BACKGROUND: Blood-testis barrier (BTB), constituted by tight junctions, adherens junctions and gap junctions, is important for spermatogenesis. PM2.5, is known to impair testicular functions and reproduction. However, its effects on BTB and the underlying mechanisms remain obscure. METHODS: In this study, we constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by PM2.5. Sprague-Dawley rats were developmentally exposed to normal saline (NS) or PM2...
November 27, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/29164306/a-structure-activity-relationship-linking-non-planar-pcbs-to-functional-deficits-of-neural-crest-cells-new-roles-for-connexins
#7
Johanna Nyffeler, Petra Chovancova, Xenia Dolde, Anna-Katharina Holzer, Vladimir Purvanov, Ilona Kindinger, Anna Kerins, David Higton, Steve Silvester, Barbara M A van Vugt-Lussenburg, Enrico Glaab, Bart van der Burg, Richard Maclennan, Daniel F Legler, Marcel Leist
Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the 'migration-inhibition of NCC (cMINC)' assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate. To address this issue, we explored here, whether the establishment of two overlapping structure-activity relationships (SAR)-linking chemical structure on the one hand to a phenotypic test outcome, and on the other hand to a mechanistic endpoint-was useful as strategy to identify relevant toxicity mechanisms...
November 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29158134/the-inflammasome-pathway-is-amplified-and-perpetuated-in-an-autocrine-manner-through-connexin43-hemichannel-mediated-atp-release
#8
Odunayo O Mugisho, Colin R Green, Dan T Kho, Jie Zhang, E Scott Graham, Monica L Acosta, Ilva D Rupenthal
BACKGROUND: Connexin43 hemichannels have been implicated in many inflammatory diseases including diabetic retinopathy (DR). Particularly, hemichannel-mediated ATP release has been associated with inflammasome pathway activation. Using an in vitro cell culture model, we evaluated hemichannel roles in response to inflammatory cytokines under high glucose (HG) conditions and propose a mechanism by which a connexin43 hemichannel-mediated autocrine ATP feedback loop augments chronic inflammatory disease...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29149200/heterozygous-deletion-of-both-sclerostin-sost-and-connexin43-gja1-genes-in-mice-is-not-sufficient-to-impair-cortical-bone-modeling
#9
Susan K Grimston, Francesca Fontana, Marcus Watkins, Roberto Civitelli
Connexin43 (Cx43) is the main gap junction protein expressed in bone forming cells, where it modulates peak bone mass acquisition and cortical modeling. Genetic ablation of the Cx43 gene (Gja1) results in cortical expansion with accentuated periosteal bone formation associated with decreased expression of the Wnt inhibitor sclerostin. To determine whether sclerostin (Sost) down-regulation might contribute to periosteal expansion in Gja1 deficient bones, we took a gene interaction approach and crossed mice harboring germline null alleles for Gja1 or Sost to generate single Gja1+/-and Sost+/-and double Gja1+/-;Sost+/-heterozygous mice...
2017: PloS One
https://www.readbyqxmd.com/read/29146153/the-stress-kinase-jnk-regulates-gap-junction-cx43-gene-expression-and-promotes-atrial-fibrillation-in-the-aged-heart
#10
Jiajie Yan, Justin K Thomson, Weiwei Zhao, Xiaomin Wu, Xianlong Gao, Dominic DeMarco, Wei Kong, Min Tong, Jun Sun, Mamdouh Bakhos, Vladimir G Fast, Qingrong Liang, Sumanth D Prabhu, Xun Ai
BACKGROUND: The stress kinase c-jun N-terminal kinase (JNK) is critical in the pathogenesis of cardiac diseases associated with an increased incidence of atrial fibrillation (AF), the most common arrhythmia in the elderly. We recently discovered that JNK activation is linked to the loss of gap junction connexin43 (Cx43) and enhanced atrial arrhythmogenicity. However, direct evidence for JNK-mediated impairment of intercellular coupling (cell-cell communication) in the intact aged atrium is lacking, as is evidence for whether and how JNK suppresses Cx43 in the aged human atrium...
November 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29134540/acute-connexin43-temporal-and-spatial-expression-in-response-to-ischemic-stroke
#11
Moises Freitas-Andrade, Jennifer She, John Bechberger, Christian C Naus, Wun Chey Sin
Connexin43 (Cx43) gap junctions expressed in astrocytes can significantly impact neuronal survival in stroke. However, little is known regarding Cx43 spatial and temporal expression during the initial stages of brain ischemia. Using immunohistochemistry and Western blot analysis, we examined Cx43 spatial and temporal expression as a function of neuronal injury within the first 24 h after permanent middle cerebral artery occlusion (pMCAO). Western blot analysis showed a significant increase in Cx43 protein expression in the core ischemic area at 2 and 3 h after pMCAO...
November 13, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29131694/role-of-neuron-glial-interaction-mediated-by-il-1%C3%AE-in-ectopic-tooth-pain
#12
H Komiya, K Shimizu, N Noma, Y Tsuboi, K Honda, K Kanno, K Ohara, M Shinoda, B Ogiso, K Iwata
Although many reports have demonstrated that ectopic pain develops in the orofacial region following tooth pulp inflammation, which often causes misdiagnosis and inappropriate treatment for patients with pulpitis, the precise mechanism remains unknown. In the present study, we hypothesized that the functional interaction between satellite glial cells and neurons mediated by interleukin 1β (IL-1β) in the trigeminal ganglion (TG) is involved in ectopic orofacial pain associated with tooth pulp inflammation...
November 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29123028/the-cell-adhesion-molecule-bt-igsf-is-essential-for-a-functional-blood-testis-barrier-and-male-fertility-in-mice
#13
Laura Pelz, Bettina Purfürst, Fritz G Rathjen
The Ig-like cell adhesion molecule (IgCAM) brain- and testis-specific immunoglobulin superfamily (BT-IgSF) protein plays a major role in male fertility in mice. However, the molecular mechanism by which BT-IgSF supports fertility is unclear. Here, we found that it is localized in Sertoli cells at the blood-testis barrier (BTB) and at the apical ectoplasmic specialization. Absence of BT-IgSF in Sertoli cells in both global and conditional mouse mutants (i.e. AMHCre and Rosa26CreERT2 lines) resulted in male infertility, atrophic testes with vacuolation, azoospermia, and spermatogenesis arrest...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29115581/tramadol-attenuates-the-sensitivity-of-glioblastoma-to-temozolomide-through-the-suppression-of-cx43%C3%A2-mediated-gap-junction-intercellular-communication
#14
Lingzhi Wang, Yuexia Peng, Jianxin Peng, Min Shao, Li Ma, Zhuoli Zhu, Guocheng Zhong, Zhengyuan Xia, Huansen Huang
Analgesics and antineoplastic drugs are often used concurrently for cancer patients. Our previous study reported that gap junctions composed of connexin32 (Cx32) was implicated in the effect of analgesics on cisplatin cytotoxicity. However, the effect of analgesic on the most widely expressed connexin (Cx), connexin43 (Cx43), and whether such effect mediates the influence on chemotherapeutic efficiency remain unknown. By manipulation of Cx43 expression or gap junction function, we found that there were gap junction-dependent and independent effect of Cx43 on temozolomide (TMZ) sensitivity in U87 glioblastoma cells...
January 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29115512/protective-effect-of-diltiazem-on-myocardial-ischemic-rats-induced-by-isoproterenol
#15
Yuejiao Wei, Tianyu Meng, Chaofeng Sun
The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague‑Dawley rats were randomly allocated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115504/upregulation-of-connexin43-by-glucose-deprivation-in-h9c2-cells-via-the-extracellular-signal%C3%A2-regulated-kinase-mitogen%C3%A2-activated-protein-kinase-signaling-pathway
#16
Guangyu Wang, Yaguang Bi, Xiangdong Liu, Meng Wei, Qingyong Zhang
Cardiac connexin43 (Cx43) serves an essential role in maintaining the functional integrity of the heart. The present study investigated the effect of glucose deprivation (GD) on Cx43 protein expression levels in H9c2 cells, and demonstrated that following 2 h GD, Cx43 protein expression levels in H9c2 cells increased by ~68%. In addition, GD activated the extracellular signal‑regulated kinase (ERK)/mitogen‑activated protein kinase (MAPK) signaling pathway, which regulated the expression levels of cardiac Cx43...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29105869/downregulation-of-spinal-astrocytic-connexin43-leads-to-upregulation-of-interleukin-6-and-cyclooxygenase-2-and-mechanical-hypersensitivity-in-mice
#17
Norimitsu Morioka, Shiori Fujii, Syun Kondo, Fang Fang Zhang, Kazuki Miyauchi, Yoki Nakamura, Kazue Hisaoka-Nakashima, Yoshihiro Nakata
Connexin43 (Cx43), involved in intercellular signaling, is expressed in spinal dorsal horn astrocytes and crucial in the maintenance of neuropathic pain. Downregulation of spinal astrocytic Cx43 in mice enhances glutamatergic neurotransmission by decreasing glutamate transporter GLT-1 expression, resulting in cutaneous hypersensitivity. Decreased expression of astrocytic Cx43 could lead to altered expression of other nociceptive molecules. Transfection of Cx43-targeting siRNA in cultured spinal astrocytes increased expression of the pronociceptive cytokine interleukin-6 (IL-6) and the prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2)...
February 2018: Glia
https://www.readbyqxmd.com/read/29101030/the-alpha2-adrenoreceptor-agonist-dexmedetomidine-protects-against-lipopolysaccharide-induced-apoptosis-via-inhibition-of-gap-junctions-in-lung-fibroblasts
#18
Yuan Zhang, Xiaoming Tan, Lianfang Xue
The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43)...
October 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29066951/connexin43-and-pannexin-based-channels-in-neuroinflammation-and-cerebral-neuropathies
#19
REVIEW
Denis Sarrouilhe, Catherine Dejean, Marc Mesnil
Connexins (Cx) are largely represented in the central nervous system (CNS) with 11 Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can form hemichannels (HCs) at non-junctional membrane as does the related channel-forming Pannexin1 (Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs appears to be involved in inflammation and has been documented in various CNS pathologies. Over recent years, evidence has accumulated supporting a link between inflammation and cerebral neuropathies (migraine, Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder, autism spectrum disorder (ASD), epilepsy, schizophrenia, bipolar disorder)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29064078/defective-wnt3-expression-by-testicular-sertoli-cells-compromise-male-fertility
#20
Sayon Basu, Satya Pal Arya, Abul Usmani, Bhola Shankar Pradhan, Rajesh Kumar Sarkar, Nirmalya Ganguli, Mansi Shukla, Kamal Mandal, Surendra Singh, Kanchan Sarda, Subeer S Majumdar
Testicular Sertoli cells make a niche for the division and differentiation of germ cells. Sertoli cells respond to increased follicle-stimulating hormone (FSH) and testosterone (T) levels at the onset of puberty by producing paracrine factors which affect germ cells and trigger robust onset of spermatogenesis. Such paracrine support to germ cells is absent during infancy, despite Sertoli cells being exposed to high FSH and T within the infant testis. This situation is similar to certain cases of male idiopathic infertility where post-pubertal Sertoli cells fail to support germ cell division and differentiation in spite of endogenous or exogenous hormonal support...
October 24, 2017: Cell and Tissue Research
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