Article
Biochemistry & Molecular Biology
Jana Gaburjakova, Marta Gaburjakova
Summary: Dantrolene is an intracellular skeletal muscle relaxant used for the treatment of malignant hyperthermia. It acts by inhibiting the RyR1 channel, preventing abnormal calcium release. However, the RyR2 channel, mainly expressed in the heart, is unresponsive to dantrolene, except under certain pathological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Luuk R. van den Bersselaar, Nick Kruijt, Gert-Jan Scheffer, Lucas van Eijk, Ignacio Malagon, Stan Buckens, Jose A. E. Custers, Leonie Helder, Anna Greco, Leo A. B. Joosten, Baziel G. M. van Engelen, Nens van Alfen, Sheila Riazi, Susan Treves, Heinz Jungbluth, Marc M. J. Snoeck, Nicol C. Voermans
Summary: This study aims to investigate the comprehensive neuromuscular and multisystem features of RYR1-related MH and ERM, establishing a well-characterized baseline cohort for future research. The study includes questionnaire surveys, clinical observations, imaging, and immunological studies.
Article
Multidisciplinary Sciences
Daniel P. Singh, Luke Pearce, Rocky H. Choi, Aldo Meizoso-Huesca, Stefan G. Wette, John W. Scott, Cedric R. Lamboley, Robyn M. Murphy, Bradley S. Launikonis
Summary: Resting skeletal muscle generates heat for endothermy in mammals but not amphibians, through the regulation of Ca2+ and the sympathetic nervous system. By studying muscle fibers in amphibians and mammals, it was found that mammals have a resistance to Ca2+-activated regenerative Ca2+ release and heat generation is regulated by cAMP-activated RyR Ca2+ leak. This indicates that the loss of a Ca2+-sensitive RyR isoform was an important evolutionary event for heat generation in mammals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Aldo Meizoso-Huesca, Luke Pearce, Christopher J. Barclay, Bradley S. Launikonis
Summary: This study reveals the role of RyR1 Ca2+ leak in generating heat at SR Ca2+ pump in resting muscle. The RyR1 Ca2+ leak increases cytosolic [Ca2+] near SR Ca2+ pump, amplifying thermogenesis. The gene-dose-dependent increase in RyR1 leak leads to progressive rise in leak-dependent heat. Moreover, fibers from mice exhibit greater basal RyR Ca2+ leak and heat generated by SR Ca2+ pump compared to toads.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Michio Matsunobe, Norio Motohashi, Eito Aoki, Tsukasa Tominari, Masaki Inada, Yoshitsugu Aoki
Summary: Caveolin-3 plays a role in muscle cells and its overexpression is associated with muscle diseases. Suppression of Cav3 expression impairs myoblast differentiation and leads to increased intracellular Ca2+ and CaMKII levels. Inhibition of the Ryanodine receptor can rescue the impaired myoblast differentiation caused by Cav3 knockdown.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stefan G. Wette, Graham D. Lamb, Robyn M. Murphy
Summary: CAPN3 is a muscle-specific member of the calpain family, which can be autolytically activated by Na+ ions in the absence of Ca2+ under non-physiological conditions. CAPN3 undergoes autolysis in the presence of high [Na+], but only when all K+ ions are absent. CAPN3 is also autolytically activated by Ca2+ in human muscle homogenates, and after autolysis, it unbinds from titin and becomes diffusible. Activation of CAPN3 does not cause proteolysis of RyR1 in physiological conditions, contrary to a previous report.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Takuya Kobayashi, Nagomi Kurebayashi, Takashi Murayama
Summary: The Ryanodine receptor (RyR) is a crucial Ca2+ release channel in skeletal and cardiac muscles, regulated by various intracellular factors. Changes in conditions such as exercise, fatigue, and disease states can alter RyR channel activity, indicating its potential role as a sensor for intracellular environment changes in muscles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Pamela V. Andrade, Joilson M. Santos, Anne C. B. Teixeira, Vanessa F. Sogari, Michelle S. Almeida, Fabiano M. Callegari, Ana C. V. Krepischi, Acary S. B. Oliveira, Mariz Vainzof, Helga C. A. Silva
Summary: In this report, an 18-year-old male patient with a cervical nodule was found to have rhabdomyosarcoma in the ethmoidal sinus. The patient's positive in vitro contracture test for malignant hyperthermia (MH) and the presence of cores in muscle histopathological analysis suggest a possible association between rhabdomyosarcomas and MH susceptibility in patients with RYR1 variants. Molecular analysis further identified germline variants in the RYR1 and ASPSCR1 genes.
Article
Anesthesiology
Lourdes Figueroa, Natalia Kraeva, Carlo Manno, Carlos A. Ibarra-Moreno, Eshwar R. Tammineni, Sheila Riazi, Eduardo Rios
Summary: By measuring sensitivity to halothane of myotubes and extending clinical observations and cell-level studies to a large group of patients, new insights into the pathological mechanism of malignant hyperthermia susceptibility have been obtained. Enhanced sensitivity to depolarisation and to halothane appear to be the primary, mutually reinforcing and phenotype-defining defects of halothane-hypersensitive patients with malignant hyperthermia susceptibility.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Article
Anesthesiology
Ruth White, Anja H. Schiemann, Sophie M. Burling, Andrew Bjorksten, Terasa Bulger, Robyn Gillies, Philip M. Hopkins, Erik-Jan Kamsteeg, Roslyn G. Machon, Sean Massey, Dorota Miller, Margaret Perry, Marc M. J. Snoeck, Jeremy Stephens, Neil Street, Luuk R. van den Bersselaar, Kathryn M. Stowell
Summary: This study identified new pathogenic variants in the RYR1 gene associated with the pharmacogenetic disorder malignant hyperthermia. Functional tests were conducted to determine the clinical relevance of these variants.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Neurosciences
Thomas R. Tripp, Barnaby P. Frankish, Victor Lun, J. Preston Wiley, Jane Shearer, Robyn M. Murphy, Martin J. MacInnis
Summary: Sprint interval training (SIT) has been found to cause fragmentation of the sarcoplasmic reticulum calcium-release channel, ryanodine receptor 1 (RyR1), 24 hours after exercise, which may serve as a signal for mitochondrial biogenesis. This study examined the time course of RyR1 fragmentation in human whole muscle and pooled type I and type II skeletal muscle fibers following a single session of SIT. Full-length RyR1 protein content was significantly lower than pre-exercise by 6 hours post-SIT in whole muscle, and fragmentation was detectable in type II but not type I fibers, albeit to a lesser extent than in whole muscle. The peak in PGC1A mRNA expression occurred earlier than RyR1 fragmentation. The increased temporal resolution and fiber type-specific responses for RyR1 fragmentation provide insights into its importance to mitochondrial biogenesis in humans.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biotechnology & Applied Microbiology
Silvia Busquets, Marta Castillejo, Queralt Jove, Baptiste Jude, Patricia Mejias, Francisco J. Lopez-Soriano, Josep M. Argiles
Summary: The study aimed to investigate the effects of combined formoterol and dantrolene treatment on body weight loss and cachexia in tumor-bearing animals. Results showed formoterol reduced muscle weight loss significantly, while dantrolene had no effect on any parameters studied. The combination treatment did not provide any additional benefits in this preclinical cachectic model.
ONCOTARGETS AND THERAPY
(2021)
Article
Clinical Neurology
Luuk R. van den Bersselaar, Nens van Alfen, Nick Kruijt, Erik-Jan Kamsteeg, Miguel A. Fernandez-Garcia, Susan Treves, Sheila Riazi, Chu-Ya Yang, Ignacio Malagon, Lucas T. van Eijk, Baziel G. M. van Engelen, Gert-Jan Scheffer, Heinz Jungbluth, Marc M. J. Snoeck, Nicol C. Voermans
Summary: A muscle ultrasound study on 40 patients with RYR1 variants associated with MH susceptibility revealed that 38% had abnormal ultrasound results, 10% had borderline results, and 53% had normal results. Muscle hypertrophy and increased echogenicity were common abnormalities observed.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Anesthesiology
Pamela V. Andrade, Lucas S. Souza, Joilson M. Santos, Jose F. F. Alves, Claudia Lutke, Jose L. G. Amaral, Mariz Vainzof, Helga C. A. Silva
Summary: Thermoregulatory dysfunction induced by spinal cord injury may obscure the early diagnosis of malignant hyperthermia, leading to fatal outcomes.
CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE
(2022)
Article
Cell Biology
Crystal Seng, Luke Pearce, Aldo Meizoso-Huesca, Daniel P. Singh, Robyn M. Murphy, Cedric R. Lamboley, Bradley S. Launikonis
Summary: Ca2+ plays an important role in the functional and developmental regulation of mitochondria, regulating ATP resynthesis rate, the expression of PGC1a, and the generation of reactive oxygen species in skeletal muscle. Understanding the triggers for Ca2+ redistribution between intracellular compartments is crucial for determining mitochondrial Ca2+ load.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Beatrice Arosio, Graziamaria Corbi, Sergio Davinelli, Vienna Giordano, Daniela Liccardo, Antonio Rapacciuolo, Alessandro Cannavo
Summary: The medical community recognizes sex-related differences in cardiovascular disease outcomes, with pre-menopausal women generally having a better prognosis than men. Estrogens have been identified as one of the leading factors driving these differences, but estrogen replacement therapy can have adverse effects. Further research is needed to understand estrogen-related mechanisms for better prevention and treatment of cardiovascular disease in women.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Alessandro Cannavo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Federica Marzano, Daniela Liccardo, Andrea Elia, Ines Mucio, Claudio de Lucia, Anna Maria Lucchese, Erhe Gao, Nicola Ferrara, Antonio Rapacciuolo, Nazareno Paolocci, Giuseppe Rengo, Walter J. Koch, Alessandro Cannavo
Summary: This study reveals that mutation of GRK5 leads to a decline in cardiac function, increased apoptosis, and fibrosis. In vitro experiments show that restricting GRK5 inside the nucleus of cardiomyocytes increases cell death. Additionally, the K215R mutation promotes the transition into a myofibroblast phenotype in fibroblasts.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2022)
Letter
Genetics & Heredity
Cristina Peduto, Giulio Piluso, Vincenzo Nigro, Nicola Brunetti-Pierri
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Medicine, General & Internal
Nicola Ferrara, Carlo Pietro Campobasso, Sergio Cocozza, Valeria Conti, Sergio Davinelli, Maria Costantino, Alessandro Cannavo, Giuseppe Rengo, Amelia Filippelli, Graziamaria Corbi
Summary: One of the characteristics of SARS-CoV-2 infection in Italy is the significant regional differences in lethality and mortality. This study analyzed the correlation between regional differences in COVID-19 mortality and different regional care models. The findings suggest that regions with more hospital beds and fewer general practitioners had higher death rates, indicating the need for a change in the current healthcare system organization.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Juliana Gurgel-Giannetti, Lucas Santos Souza, Guilherme L. Yamamoto, Marina Belisario, Monize Lazar, Wilson Campos, Rita de Cassia M. Pavanello, Mayana Zatz, Umbertina Reed, Edmar Zanoteli, Acary Bulle Oliveira, Vilma-Lotta Lehtokari, Erasmo B. Casella, Marcela C. Machado-Costa, Carina Wallgren-Pettersson, Nigel G. Laing, Vincenzo Nigro, Mariz Vainzof
Summary: Nemaline myopathy in Brazilian patients shows significant clinical and genetic heterogeneity, with a high frequency of NEB gene mutations. There is noticeable variability in clinical presentation and MRI patterns, with respiratory involvement often being severe.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Emanuela Viggiano, Esther Picillo, Luigia Passamano, Maria Elena Onore, Giulio Piluso, Marianna Scutifero, Annalaura Torella, Vincenzo Nigro, Luisa Politano
Summary: English Summary: Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the DMD gene. A study conducted on 750 patients in southern Italy revealed that deletions were the most common variation, followed by point mutations and duplications. Next-Generation Sequencing (NGS) was found to be useful in identifying point mutations. It is important to ensure timely genetic diagnoses for DMD and BMD patients to enable appropriate treatment.
Article
Oncology
Rosina Paterra, Paola Bettinaglio, Arianna Borghi, Eleonora Mangano, Viviana Tritto, Claudia Cesaretti, Carla Schettino, Roberta Bordoni, Claudia Santoro, Sabrina Avignone, Marco Moscatelli, Mariarosa Anna Beatrice Melone, Veronica Saletti, Giulio Piluso, Federica Natacci, Paola Riva, Marica Eoli
Summary: Currently, there is a lack of systematic study on the clinical spectrum and molecular characteristics of spinal neurofibromatosis (SNF) in patients with neurofibromatosis 1 (NF1). This study provides evidence that SNF patients are at high risk of problematic neurofibromas, including bilateral neurofibromas involving all spinal roots, and a higher incidence of internal neurofibromas and nerve root swelling.
Article
Biochemistry & Molecular Biology
Annalaura Torella, Alberto Budillon, Mariateresa Zanobio, Francesca Del Vecchio Blanco, Esther Picillo, Luisa Politano, Vincenzo Nigro, Giulio Piluso
Summary: Transposon insertion in the DMD gene can cause variable clinical phenotypes of muscular dystrophy, and accurate prediction based on DNA variants is crucial for diagnosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Miriam Zacchia, Giovanna Capolongo, Francesca Del Vecchio Blanco, Floriana Secondulfo, Neha Gupta, Giancarlo Blasio, Rosa Maria Pollastro, Angela Cervesato, Giulio Piluso, Giuseppe Gigliotti, Annalaura Torella, Vincenzo Nigro, Alessandra F. F. Perna, Giovambattista Capasso, Francesco Trepiccione
Summary: In this study, NGS analysis was used to analyze the genetic causes of inherited kidney disorders in 176 individuals. Unexpected genetic results were found in 5 individuals, with 3 of them having mutations in collagen type IV genes. This study highlights the crucial role of NGS in diagnosing inherited renal disorders and demonstrates the phenotypic variability in patients with mutations in collagen type IV genes.
Review
Oncology
Cristina Peduto, Mariateresa Zanobio, Vincenzo Nigro, Silverio Perrotta, Giulio Piluso, Claudia Santoro
Summary: In recent years, there has been an increase in the description of genotype-phenotype correlations for neurofibromatosis type 1 (NF1), which affects the clinical follow-up of patients, especially children. The use of molecular diagnosis, facilitated by next generation sequencing technology, allows for early confirmation of clinical diagnosis, even in cases with atypical presentation or overlapping conditions. This article reviews the main clinical characteristics and complications of NF1, particularly in children, and discusses the genotype-phenotype associations that impact genetic counseling and prognosis. Molecular diagnosis is crucial for confirming clinical diagnoses, especially with recently revised diagnostic criteria, and for early identification of genotypes associated with specific phenotypes.
Review
Peripheral Vascular Disease
Amir Hossein Behnoush, Amirmohammad Khalaji, Pegah Bahiraie, Parsa Alehossein, Parnian Shobeiri, Maral Peisepar, Alessandro Cannavo
Summary: Hypertension is a major risk factor for cardiovascular disease and a leading cause of death worldwide. Endothelial dysfunction (ED) is an important manifestation preceding the development of hypertension. Endocan, secreted from endothelial cells, is a novel biomarker for endothelial dysfunction and inflammation. This systematic review and meta-analysis aimed to explore the association between endocan levels and ED in hypertensive patients.
HYPERTENSION RESEARCH
(2023)
Editorial Material
Biochemistry & Molecular Biology
Alessandro Cannavo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Graziamaria Corbi, Vincenzo Nobile, Valeria Conti, Alessandro Cannavo, Vincenzo Sorrenti, Alessandro Medoro, Giovanni Scapagnini, Sergio Davinelli
Summary: This study aimed to evaluate the effects of equol and resveratrol on bone turnover biomarkers in postmenopausal women. The results showed that the combination of equol and resveratrol significantly improved bone turnover biomarkers and increased bone mineral density, suggesting a potential approach to prevent age-related bone loss in postmenopausal women.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Alessandro Cannavo, Daniela Liccardo, Monica Gelzo, Felice Amato, Ivan Gentile, Biagio Pinchera, Grazia D. Femminella, Roberto Parrella, Annunziata De Rosa, Giuseppina Gambino, Federica Marzano, Nicola Ferrara, Nazareno Paolocci, Giuseppe Rengo, Giuseppe Castaldo
Summary: Elevated levels of galectin-3 and aldosterone in the serum of COVID-19 patients may have adverse effects on cardiac structure and function. These biomarkers have the potential to predict and guide the treatment of cardiac complications in COVID-19 patients.
MINERVA ENDOCRINOLOGY
(2022)