Article
Neurosciences
Xinyu Wang, Chuan Jiang, Chunli Lu, Longbing Ma, Yuxin Feng, Shengyu Cui, Qian Li, Kang Li, Xiang Wang, Fengzeng Jian
Summary: In this study, changes in the number and morphology of ependymal cilia in a syringomyelia rat model were investigated. The results showed a decline in cilia during the early stage of the disease, leading to disrupted intercellular communication. In the later stage, cilia were further reduced due to shear stress exposure, causing a potential mechanism of ependymal cilia decline in syringomyelia development.
EXPERIMENTAL NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Daniel Rodjakovic, Lilian Salm, Guido Beldi
Summary: Recent studies have shown that Connexin-43 plays important roles in macrophages, including migration, antigen-presentation, intercellular communication, electrochemical support, and immunomodulation. Dysregulation of Cx43 has been described in diseases such as inflammatory bowel disease, tumors, and HIV. However, its involvement in other macrophage functions and inflammatory processes requires further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
R. I. Jabr, S. C. Salvage, F. S. Hatch, C. H. Fry
Summary: Atrial fibrillation (AF) results from disordered atrial action potential conduction and reduced gap junction electrical conductance (G(j)). The calcineurin-dependent pathway involving protein phosphatase-1 (PP1) and phosphorylation of serine368 on connexin43 (pSer368-Cx43) is responsible for reducing G(j) in ventricular myocardium, but the corresponding pathways in left atrial myocardium, with a more complex connexin subtype profile, are still undefined. This study aims to characterize these pathways. The results show that low-Na solution reduces G(j) in guinea-pig left atrium, but this reduction is attenuated or prevented by calcineurin inhibitors cyclosporin-A or CAIP, respectively. Furthermore, the phosphorylation of Ser368-Cx43 in low-Na solution is also prevented by CAIP. Changes in Cx43/Cx40 phosphorylation status with raised intracellular [Ca2+](i) are mediated by calcineurin and PP2A-dependent pathways rather than PP1.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Cell Biology
Weiqi Zeng, Zhizhao Deng, Yingxin Gao, Guoliang Sun, Xianlong Li, Dongdong Yuan
Summary: Long-term exposure to Ang II significantly enhances the expression and function of Cx43-GJs in HUASMCs, leading to the accumulation of intracellular Ca2+ and the activation of downstream signaling pathways. However, propofol inhibits the function of Cx43-GJs in Ang II-pretreated HUASMCs, resulting in the inhibition of intracellular Ca2+ and its downstream signaling pathways and ultimately excessive relaxation of HUASMCs. This explains why patients with chronic hypertension experience more severe blood pressure fluctuations after propofol induction.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biology
Filippo Torrisi, Cristiana Alberghina, Debora Lo Furno, Agata Zappala, Samuel Valable, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti
Summary: Manipulating the sonic hedgehog pathway to affect connexin 43 expression can regulate cell migration and proliferation in glioblastoma, potentially offering a new therapeutic strategy.
Article
Medicine, Research & Experimental
Huiqin Wang, Xueying Yang, Huaqing Lai, Yang Sun, Xu Yan, Qidi Ai, Meiyu Lin, Songwei Yang, Yantao Yang, Shifeng Chu, Zhenzhen Wang, Naihong Chen
Summary: Hypericin repaired the dysfunction of gap junctions in the chronic unpredictable stress (CUS) rat model of depression. While hypericin showed potential for treating depression in in vivo experiments, it failed to demonstrate antidepressant benefits in cell experiments. This study suggests that gap junctional function may be a novel therapeutic target for hypericin in the treatment of depression.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Physiology
Aya Yamada, Keigo Yoshizaki, Masaki Ishikawa, Kan Saito, Yuta Chiba, Emiko Fukumoto, Ryoko Hino, Seira Hoshikawa, Mitsuki Chiba, Takashi Nakamura, Tsutomu Iwamoto, Satoshi Fukumoto
Summary: Connexin 43 (Cx43) is an integral membrane protein that plays a crucial role in tooth development, regulating intercellular communication through gap junction activity by modulating TGF-beta 1-mediated ERK signaling and enamel formation.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yan-Jun Zong, Xiao-Zhou Liu, Lei Tu, Yu Sun
Summary: This review discusses the contribution of the connexin gene family to hearing loss, focusing on the GJB2, GJB6, and GJA1 genes. Mutations in these genes can lead to comprehensive or non-comprehensive genetic deafness in newborns. The precise regulation of connexin biosynthesis, structural composition, and degradation is crucial for proper functioning of gap junctions. This review provides insights into the etiological principles of connexin mutations and offers potential therapeutic strategies for hereditary deafness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Chao Qi, Silvia Acosta Gutierrez, Pia Lavriha, Alaa Othman, Diego Lopez-Pigozzi, Erva Bayraktar, Dina Schuster, Paola Picotti, Nicola Zamboni, Mario Bortolozzi, Francesco Luigi Gervasio, Volodymyr M. Korkhov
Summary: In this study, the structure of a human Cx43 GJC was determined using cryo-EM and single particle analysis. The pore region of Cx43 GJC was found to have lipid-like densities, and a previously undescribed conformation was discovered on the cytosolic side of the pore. Molecular dynamics simulations revealed the channel properties of Cx43. The captured states of Cx43 were consistent with a closed state.
Article
Agriculture, Multidisciplinary
Ying-Xin Zhao, Yi-Xi Tang, Xiao-Han Sun, Shi-Yong Zhu, Xue-Yan Dai, Xue-Nan Li, Jin-Long Li
Summary: This study utilized an in vivo model of neurotoxicity in quail to investigate the effects of DEHP exposure on astrocytes. The results revealed that DEHP exposure resulted in phosphorylation and translocation of Cx43 in astrocytes. Additionally, the study showed that DEHP exposure induced pro-inflammatory status and autophagosome formation in astrocytes. These findings provide valuable insights into the mechanisms of neurodegeneration caused by DEHP exposure and suggest a potential therapeutic target for its treatment.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Dentistry, Oral Surgery & Medicine
Wen Yi Lim, Leigh Edward Madden, David Laurence Becker
Summary: This study observed an upregulation of Cx43 throughout the pulpal stroma as inflammation worsened in both human and rodent models. Elevated levels of neutrophils were present in advanced pulpitis. In human samples, apoptosis and necroptosis appeared to be upregulated as Cx43 levels rose.
CLINICAL ORAL INVESTIGATIONS
(2021)
Article
Neurosciences
Chelsea M. Phillips, Allison M. Johnson, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: This study reveals that the absence of CCM3 leads to structural defects in the brain endothelial barrier, increasing the risk of vascular leakage. The upregulation of GJA1-20 k is found to disrupt the balance between gap junctions and tight junctions, destabilizing the tight junction complex and increasing brain endothelial barrier permeability.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Zhizhao Deng, Yanling Zhang, Qian Zhang, Xianlong Li, Weiqi Zeng, Cai Jun, Dongdong Yuan
Summary: The study showed that Cx43-GJs play a key role in Ang II-induced contraction of HUASMCs, potentially regulating intracellular Ca2+ mobility as well as RhoA/LIMK2/Cofilin signaling pathway activity. Propofol can reverse the effects induced by Ang II by inhibiting the function of Cx43-GJs.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Food Science & Technology
Dong-Hoon Won, Da -Bin Hwang, Changuk Kim, MinHwa Kang, Young Jeon, Yong Il Park, Jeong-Hwan Che, Jun-Won Yun
Summary: Gap junctional intercellular communication (GJIC), composed of connexin (Cx), plays a crucial role in maintaining intracellular homeostasis. This study investigated the impact of the genotoxic carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), as a representative PAH, on GJIC and found that it suppresses GJIC by inhibiting both post-transcriptional and post-translational processing of Cx43. The results suggest that GJIC assay can serve as an efficient short-term screening test for predicting the carcinogenic potential of genotoxic carcinogens.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Cai Qing, Zhao Xinyi, Yu Xuefei, Xue Xindong, Fu Jianhua
Summary: Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants, characterized by alveolar maldevelopment associated with oxidative stress and excessive apoptosis. Gap26, a connexin 43-inhibiting peptide, has been shown to improve alveolar development by inhibiting intercellular communication in BPD.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Samantha C. Salvage, Esther M. Gallant, Nicole A. Beard, Shiraz Ahmad, Haseeb Valli, James A. Fraser, Christopher L. -H. Huang, Angela F. Dulhunty
JOURNAL OF CELL SCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Samantha C. Salvage, Wandi Zhu, Zaki F. Habib, Soyon S. Hwang, Jennifer R. Irons, Christopher L. H. Huang, Jonathan R. Silva, Antony P. Jackson
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Physiology
Maria S. Espejo, Alejandro Orlowski, Alejandro M. Ibanez, Romina A. Di Mattia, Fernanda Carrizo Velasquez, Noelia S. Rossetti, Maria C. Ciancio, Veronica C. De Giusti, Ernesto A. Aiello
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Samantha C. Salvage, Johanna S. Rees, Alexandra McStea, Michael Hirsch, Lin Wang, Christopher J. Tynan, Matthew W. Reed, Jennifer R. Irons, Richard Butler, Andrew J. Thompson, Marisa L. Martin-Fernandez, Christopher L-H Huang, Antony P. Jackson
Article
Medicine, Research & Experimental
Romina A. Di Mattia, Juan I. E. Mariangelo, Paula G. Blanco, Carolina Jaquenod De Giusti, Enrique L. Portiansky, Cecilia Mundina-Weilenmann, Ernesto A. Aiello, Alejandro Orlowski
Article
Medicine, Research & Experimental
Alejandro Orlowski, Michael G. Katz, Sarah M. Gubara, Anthony S. Fargnoli, Kenneth M. Fish, Thomas Weber
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2020)
Article
Multidisciplinary Sciences
Khalil Saadeh, Zakaria Achercouk, Ibrahim T. Fazmin, Nakulan Nantha Kumar, Samantha C. Salvage, Charlotte E. Edling, Christopher L-H Huang, Kamalan Jeevaratnam
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Samantha C. Salvage, Christopher L. -H. Huang, Antony P. Jackson
Article
Cell Biology
Samantha C. Salvage, Esther M. Gallant, James A. Fraser, Christopher L-H Huang, Angela F. Dulhunty
Summary: Research suggests that flecainide has complex effects on RyR2 channels, with different regulatory actions on channels with different open probabilities, exhibiting a dual mechanism of activation and inhibition.
Review
Biochemistry & Molecular Biology
Samantha C. Salvage, Zaki F. Habib, Hugh R. Matthews, Antony P. Jackson, Christopher L. -H. Huang
Summary: The activation of voltage-dependent Na+ channels plays a crucial role in cellular excitability through action potential generation. This review discusses the potential feedback actions of intracellular [Ca2+] on Na+ channel activity, highlighting their structural, genetic, cellular, and functional implications and their possible clinical importance. Studies on Na+ channel mutations associated with skeletal and cardiac muscle diseases, as well as the effects of cytoplasmic [Ca2+] on channel gating, provide insight into potential therapeutic strategies for arrhythmic conditions such as catecholaminergic polymorphic ventricular tachycardia.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Physiology
Samantha C. Salvage, Christopher L. -H. Huang, James A. Fraser, Angela F. Dulhunty
Summary: Flecainide, an antiarrhythmic drug, can reduce calcium ion release in the heart through multiple molecular mechanisms. It plays an important role in the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT).
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Review
Neurosciences
Samantha C. Salvage, Kamalan Jeevaratnam, Christopher L. -H. Huang, Antony P. Jackson
Summary: The paragraph discusses the role of the beta 1 and beta 3 subunits in regulating the Na(V)1.5 sodium channel in cardiac myocytes, and how specific mutations in these subunits are associated with inherited cardiac arrhythmias. It also highlights new structural insights that raise questions about the physiological function of these proteins.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Cell Biology
Samantha C. Salvage, Taufiq Rahman, David A. Eagles, Johanna S. Rees, Glenn F. King, Christopher L-H. Huang, Antony P. Jackson
Summary: This study investigates the influence and modulation of the Na-V-beta 3-subunit on the function of the voltage-gated sodium channel Na(V)1.7 and the effect of the toxins ProTx-II and OD1 on Na(V)1.7 function. The results show that ProTx-II slows the activation rate of Na(V)1.7, while OD1 reduces fast inactivation rate and accelerates recovery from inactivation. The presence of the beta 3-subunit partially counteracts these effects. Furthermore, OD1 induces a hyperpolarising shift in the steady-state activation voltage of Na(V)1.7, which is not observed in the presence of beta 3. The study suggests that the beta 3-subunit influences the interaction between toxins and Na(V)1.7 through indirect allosteric mechanisms.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Biology
Samantha C. C. Salvage, Angela F. F. Dulhunty, Kamalan Jeevaratnam, Antony P. P. Jackson, Christopher L. -H. Huang
Summary: Skeletal and cardiac muscle excitation-contraction coupling involves the interaction between Na(v)1.4/Na(v)1.5 and Cav1.1/Cav1.2 channels, as well as RyR1/RyR2 receptors, mediated by SR Ca2+ release. Studies have shown the potential feedback actions of SR Ca2+ release on Na(v)1.4/Na(v)1.5 function. Experimental observations have revealed the effects of RyR inhibitors and activators on Na+ currents in muscle fibers and cardiomyocytes. The modulation of Ca2+ transients and AP conduction has implications for arrhythmogenicity.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Samantha C. Salvage, Karthik H. Chandrasekharan, Kamalan Jeevaratnam, Angela F. Dulhunty, Andrew J. Thompson, Antony P. Jackson, Christopher L-H Huang
BRITISH JOURNAL OF PHARMACOLOGY
(2018)