Article
Cell Biology
Jing-Jun Zhao, Zheng-Hui Wang, Ying-Jie Zhang, Wen-Jing Wang, Ai-Fang Cheng, Pei-Jing Rong, Chun-Lei Shan
Summary: This study investigated the impact of auricular vagus nerve stimulation on the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury. The findings suggested that the stimulation can promote recovery by altering the secretion of acetylcholine and inflammatory factors, as well as the phosphorylation of connexin 43.
NEURAL REGENERATION RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Sin Hang Crystal Chan, Jarred M. Griffin, Connor A. Clemett, Margaret A. Brimble, Simon J. O'Carroll, Paul W. R. Harris
Summary: Peptide5 is a mimetic peptide with 12 amino acids that plays an important role in cell-to-cell communication. In order to improve its activity and stability, twenty-five novel mimetics were designed and synthesized. The results showed that one variant, H-VDCFLSRPTE-N-MeKT-OH, exhibited good activity and stability.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Erin M. O'Shaughnessy, William Duffy, Laura Garcia-Vega, Keith Hussey, A. David Burden, Mozheh Zamiri, Patricia E. Martin
Summary: Elevated expression of Connexin26 in psoriatic tissue may contribute to cellular events imbalance, while inhibition of Connexin signaling reduces pro-inflammatory events and may have therapeutic benefits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Antonio Cibelli, Sandra Veronica Lopez-Quintero, Sean Mccutcheon, Eliana Scemes, David C. Spray, Randy F. Stout, Sylvia O. Suadicani, Mia M. Thi, Marcia Urban-Maldonado
Summary: The study successfully transduced mouse cortical astrocytes using a lentiviral vector encoding hTERT, generating immortalized cell lines with characteristics consistent with neonatal astrocytes. These cell lines showed stability in the expression of astrocyte-specific markers over cell passages.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Zuping Wu, Chenchen Zhou, Quan Yuan, Demao Zhang, Jing Xie, Shujuan Zou
Summary: CTGF promotes intercellular communication in chondrocytes through upregulating Cx43 expression and activating the PI3K/Akt signaling pathway.
CELL PROLIFERATION
(2021)
Article
Reproductive Biology
Lin Yin, Wusu Wang, Weijun Pang, Gongshe Yang, Lei Gao, Guiyan Chu
Summary: Gap junction intercellular communication plays an important role in follicular development. In porcine follicles, Cx43 is the most widely expressed connexin. Insulin can enhance Cx43 protein expression, which is dependent on the phosphorylated activities of AKT and Erk.
Article
Biochemistry & Molecular Biology
Daniela Madeira, Joana Domingues, Catia R. Lopes, Paula M. Canas, Rodrigo A. Cunha, Paula Agostinho
Summary: Increasing evidence suggests that dysfunction of astrocytes, a type of glial cell, plays a role in the development of Alzheimer's disease. This dysfunction is characterized by altered astrocytic morphology and increased activity of astrocytic hemichannels, which are composed mainly of connexin 43 (Cx43). The activity of these hemichannels is found to be modulated by adenosine A2A receptor (A2AR), and blocking A2AR can prevent the dysregulation of astrocytic hemichannels induced by amyloid-beta (Aβ) plaques. Overall, our findings indicate that the dysfunction of astrocytic hemichannel activity is an early event in Alzheimer's disease and can be controlled by targeting A2AR.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kristina Rode, Marion Langeheine, Bettina Seeger, Ralph Brehm
Summary: Studies have shown that Cx43 in spermatogonia/spermatids is not essential for successful termination of spermatogenesis, and using a GC-specific Cx43 KO does not affect fertility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Raghda Ramadan, Sarah Baatout, An Aerts, Luc Leybaert
Summary: Radiation therapy is effective in treating breast cancer and other thoracic tumors, but can lead to secondary cardiovascular diseases due to radiation exposure of the heart and large arteries. Radiation-induced coronary artery atherosclerosis is a major cardiovascular complication in thoracic radiotherapy-treated patients, with complex biological and molecular mechanisms that are not fully understood. Ionizing radiation exposure can damage the vascular endothelium, leading to atherosclerosis through various mechanisms such as DNA damage, oxidative stress, cellular senescence, and inflammation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Cell Biology
Stefan Dhein, Aida Salameh
Summary: The heart relies on gap junction channels to maintain cell-cell coupling for efficient and rapid electrical conduction. Connexin expression and gap junction localization play crucial roles in modulating cardiac electrical properties, ultimately affecting cardiac stability and function.
Review
Biochemistry & Molecular Biology
Tania Martins-Marques, Derek J. Hausenloy, Joost P. G. Sluijter, Luc Leybaert, Henrique Girao
Summary: Cell-to-cell communication plays a crucial role in maintaining tissue homeostasis, and disruptions in this communication have been implicated in harmful consequences of heart ischemia and reperfusion, such as arrhythmias and heart failure. Targeting intercellular communication mechanisms may offer potential therapeutic strategies to prevent or repair these consequences and restore myocardial function.
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Neurosciences
Yujia Zhao, Yuze Qi, Qingru Li, Huihui Quan, Dan Liu, Hui Zhou
Summary: This study used an in vivo Parkinson's disease model to investigate the role of Cx43 and its underlying mechanisms. The results showed that inhibiting Cx43 may prevent neurotoxicity and dopaminergic neuronal death caused by lipopolysaccharide, possibly by reducing neuroinflammation and increasing neurotrophic factors.
NEUROSCIENCE LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Lang Cai, Caixia Pi, Daimo Guo, Jiazhou Li, Hao Chen, Demao Zhang, Xuedong Zhou, Jing Xie
Summary: This study reveals that TGF-03 plays a promoting role in gap-junction mediated intercellular communication in chondrocytes. It enhances cell-to-cell communication by up-regulating Cx43. TGF-03-induced cell-to-cell communication requires the involvement of TGF-beta type I receptor ALK5 and relies on the activation of p-Smad3 signaling. These findings provide a new perspective on the importance of TGF-03 in cartilage physiology and pathobiology.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Oncology
Jie Zhang, Colin R. Green, Odunayo O. Mugisho
Summary: Cell transdifferentiation involves the conversion of one cell type to another without passing through a pluripotent cell state, and includes processes such as epithelial- and endothelial-mesenchymal transition. These processes can occur during embryonic development and wound healing, but can also be pathological. The role of connexins in these processes in the eye and related diseases suggests potential for therapeutic intervention.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Olivia E. Crouthamel, Leping Li, Michael T. Dilluvio, Thomas W. White
Summary: Mutations in the GJA1 gene encoding connexin43 (Cx43) have been linked to various rare genetic disorders, including those affecting the skin. This study investigated the functional consequences of a specific Cx43 mutation (Cx43-G38E) associated with a novel human phenotype. The research showed that the mutation increased the activity of hemichannels, suggesting a potential role in skin and skeletal disorders caused by Cx43 mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Claudia Garcia-Rodriguez, Ivan D. Bravo-Tobar, Yorley Duarte, Luis C. Barrio, Juan C. Saez
Summary: Overcoming refractory epilepsy's resistance to medication, reducing side effects, and preventing sudden unexpected death are crucial therapeutic goals. This review emphasizes the involvement of non-selective membrane channels and receptors in epilepsy, highlighting their activation and contribution to seizure intensity.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Juan Guiza, Javiera Arriagada, Luis Rodriguez, Camila Gutierrez, Yorley Duarte, Juan C. Saez, Jose L. Vega
Summary: Proteins connexins, innexins, and pannexins are subunits of non-selective channels found in vertebrates and invertebrates' cell membranes, participating in physiological and pathophysiological processes. Some anti-parasitic drugs can block these channels, potentially explaining their effects on parasitic infections. Studies have also shown the presence of these proteins in various parasites causing infections.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Juan Guiza, Anibal Garcia, Javiera Arriagada, Camila Gutierrez, Jorge Gonzalez, Valeria Marquez-Miranda, Melissa Alegria-Arcos, Yorley Duarte, Maximiliano Rojas, Fernando Gonzalez-Nilo, Juan C. Saez, Jose L. Vega
Summary: The study identified innexin protein homologs in unicellular organisms, which may serve as protein subunits of novel large-pore channels in single-celled organisms. These proteins were found to have key structural features and potential functional roles similar to those in parasitic diseases like Chagas.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arlek Gonzalez-Jamett, Walter Vasquez, Gabriela Cifuentes-Riveros, Rafaela Martinez-Pando, Juan C. Saez, Ana M. Cardenas
Summary: Muscular dystrophies are a heterogeneous group of neuromuscular disorders characterized by muscle pain, weakness, and atrophy. These diseases are caused by gene mutations that affect the structure and function of skeletal muscles, leading to inflammation, oxidative stress, and muscle degeneration. Dysregulation of connexin hemichannels plays a crucial role in these processes.
Article
Neurosciences
Cristian Arredondo, Carolina Cefaliello, Agnieszka Dyrda, Nur Jury, Pablo Martinez, Ivan Diaz, Armando Amaro, Helene Tran, Danna Morales, Maria Pertusa, Lorelei Stoica, Elsa Fritz, Daniela Corvalan, Sebastian Abarzua, Maxs Mendez-Ruette, Paola Fernandez, Fabiola Rojas, Meenakshi Sundaram Kumar, Rodrigo Aguilar, Sandra Almeida, Alexandra Weiss, Fernando J. Bustos, Fernando Gonzalez-Nilo, Carolina Otero, Maria Florencia Tevy, Daryl A. Bosco, Juan C. Saez, Thilo Kahne, Fen-Biao Gao, James D. Berry, Katharine Nicholson, Miguel Sena-Esteves, Rodolfo Madrid, Diego Varela, Martin Montecino, Robert H. Brown, Brigitte van Zundert
Summary: Non-cell-autonomous mechanisms, specifically the release of unidentified toxic factors by astrocytes, contribute to the neurodegenerative diseases ALS and FTD. Studies found that astrocytes with ALS/FTD-related mutations display elevated levels of intracellular inorganic polyphosphate (polyP), which is also present in astrocyte-conditioned media (ACM). Degradation or neutralization of polyP in ALS/FTD astrocytes or ACM prevents the death of motoneurons. Additionally, polyP staining signals are enriched in postmortem ALS spinal cord sections and ALS cerebrospinal fluid (CSF) exhibits increased concentrations of polyP, suggesting polyP as a potential therapeutic target and biomarker for ALS/FTD.
Article
Multidisciplinary Sciences
Nicolas Palacios-Prado, Paola A. Soto, Ximena Lopez, Eun Ju Choi, Valeria Marquez-Miranda, Maximiliano Rojas, Yorley Duarte, Jinu Lee, Fernando D. Gonzalez-Nilo, Juan C. Saez
Summary: The study revealed that Pannexin1 forms cell-cell channels with distinct phenotypes and properties, exhibiting high conductivity and sensitivity to voltage and temperature; bioinformatics studies suggested that arginine residues inside the channel pore may be neutralized by hydrophobic interactions, allowing the passage of certain substances.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Nutrition & Dietetics
Antonia Recabal, Sergio Lopez, Magdiel Salgado, Alejandra Palma, Ana M. Obregon, Roberto Elizondo-Vega, Juan C. Saez, Maria A. Garcia-Robles
Summary: Radial glia-like cells in the hypothalamus and dorsal vagal complex are neural precursors that can detect blood-borne nutrients and hormones and increase their proliferation in response to a high-fat diet. This study found that a short-term high sucrose diet can also increase the proliferation of these precursors, while fructose alone does not have the same effect as glucose.
Article
Biochemistry & Molecular Biology
Claudia M. Lucero, Lucas Marambio-Ruiz, Javiera Balmazabal, Juan Prieto-Villalobos, Marcelo Leon, Paola Fernandez, Juan A. Orellana, Victoria Velarde, Juan C. Saez, Gonzalo Gomez
Summary: This study found that the activation of Cx43 hemichannels and inhibition of cell-cell coupling during inflammation may contribute to oxidative stress and damage of mesangial cells through the RhoA/ROCK pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Anni Guo, Huiqi Zhang, Huanhuan Li, Arthur Chiu, Claudia Garcia-Rodriguez, Carlos F. Lagos, Juan C. Saez, Chunyue Geoffrey Lau
Summary: Temporal lobe epilepsy is a common type of epilepsy, but many patients are resistant to current drugs. Dysfunction of astrocytes and microglia is related to neuroinflammation and hyperexcitability. This study introduces a new compound, D4, that targets glial hemichannels, leading to improved symptoms and survival rates in a mouse model of epilepsy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Ana C. Abbott, Isaac E. Garcia, Felipe Villanelo, Carolina Flores-Munoz, Ricardo Ceriani, Jaime Maripillan, Joel Novoa-Molina, Cindel Figueroa-Cares, Tomas Perez-Acle, Juan C. Saez, Helmuth A. Sanchez, Agustin D. Martinez
Summary: It has been demonstrated that a genetic mutation in the gap junction protein Connexin 26 (Cx26) can lead to hyperactivity and damage of hearing cells in the cochlea, resulting in syndromic deafness. The specific mutation Cx26S17F, when co-expressed with wild-type connexins like Cx30, forms hyperactive hemichannels in supporting cells of the organ of Corti. These hyperactive hemichannels are insensitive to blockers and ions, leading to abnormal calcium influx and cellular damage.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Jose L. Vega, Camila Gutierrez, Mauro Rojas, Juan Guiza, Juan C. Saez
Summary: Plasma membrane ionic channels selectively permeate potassium, sodium, calcium, and chloride ions. Large-pore channels, formed by various proteins, are permeable to ions and small molecules, and play crucial roles in inflammatory responses, including the activation of inflammasomes and the release of pro-inflammatory cytokines and ATP. This review provides an overview of the current understanding of large-pore channels and their contribution to inflammation induced by microorganisms, virulence factors, or their toxins.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Luis A. Cea, Walter Vasquez, Romina Hernandez-Salinas, Alejandra Z. Vielma, Mario Castillo-Ruiz, Victoria Velarde, Magdiel Salgado, Juan C. Saez
Summary: Individuals with diabetes mellitus experience skeletal muscle myopathy characterized by atrophy. The mechanism behind this muscular alteration is unclear, making it difficult to design effective treatments. In this study, it was found that boldine, a compound that inhibits non-selective channels, prevented skeletal muscle fiber atrophy in diabetic rats. This was attributed to the blocking of connexin hemichannels and P2X(7) receptors. Additionally, boldine prevented high glucose-induced increase in sarcolemma permeability and expression of NLRP3, suggesting that it could potentially be used as a therapeutic agent for muscular complications in diabetes.
Review
Biochemistry & Molecular Biology
Claudia Garcia-Rodriguez, Paula Mujica, Javiera Illanes-Gonzalez, Araceli Lopez, Camilo Vargas, Juan C. Saez, Arlek Gonzalez-Jamett, Alvaro O. Ardiles
Summary: Probenecid, an old uricosuric agent, has been used to treat gout and reduce renal excretion of antibiotics. Recent studies have shown that Probenecid has the ability to interact with membrane proteins, indicating potential therapeutic applications in medicine. It has been found to have neuroprotective, antiepileptic, and anti-inflammatory properties, making it useful in the treatment of neurological and neurodegenerative diseases. Despite its declining clinical use, Probenecid shows promise in preclinical research as a strategy to enhance drug bioavailability in the central nervous system.
Article
Multidisciplinary Sciences
Juan Guiza, Francisco Solis, Bernardita Valenzuela, Duxan Arancibia, Pedro Zamorano, Jorge Gonzalez, Jonathan Saavedra, Alan Neely, Magdiel Salgado, Agustin D. Martinez, Juan C. Saez, Jose L. Vega
Summary: Cells of vertebrate and invertebrate organisms communicate through membrane channels specialized in cell-cell communication, which are absent in unicellular organisms. This study discovered a family of large-pore channel proteins called unnexins in kinetoplastids, which share similarities with innexin and pannexin proteins. Specifically, the unnexin1 protein (Unx1) forms membrane channels that allow the influx of Ca2+. Low extracellular Ca2+/Mg2+ levels or extracellular alkalinization increase Unx1 channel activity, while mechanical stretching does not have this effect. Unx1 also plays a role in cell invasion and can be a potential target for developing drugs to treat Trypanosoma cruzi infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.