Article
Pharmacology & Pharmacy
Serena Van, Soumiya Pal, Brittney R. Garner, Kate Steed, Vijayalakshmi Sridharan, Shengyu Mu, Nancy J. Rusch, Amanda J. Stolarz
Summary: The study showed that dantrolene could prevent the detrimental effects of doxorubicin on lymphatic function, reducing the risk of lymphedema in patients undergoing doxorubicin chemotherapy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Jesus M. Aizpurua, Jose Miranda, Aitziber Irastorza, Endika Torres, Maite Eceiza, Maialen Sagartzazu-Aizpurua, Pablo Ferron, Garazi Aldanondo, Haizpea Lasa-Fernandez, Pablo Marco-Moreno, Naroa Dadie, Adolfo Lopez de Munain, Ainara Vallejo-Illarramendi
Summary: The study investigated the hypothesis of rescuing FKBP12/RyR1 interaction and intracellular calcium homeostasis through molecular reshaping of FKBP12. Novel triazoles were designed and synthesized, showing potential as therapeutic candidates for muscle disorders with nitro-oxidative stress, FKBP12/RyR1 dysfunction, and calcium dysregulation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Hua Zhang, Caitlynn Knight, S. R. Wayne Chen, Ilya Bezprozvanny
Summary: It has been found that RyanR is overactive in Alzheimer's disease (AD) and inhibiting RyanR may be beneficial for AD treatment. This study investigated the potential connection between basal RyanR activity and autophagy in neurons. The results showed that the basal RyanR2 activity inhibited autophagy through the calcineurin-AMPK-ULK1 pathway, and increased basal RyanR2 activity in AD may lead to the inhibition of neuronal autophagy and accumulation of β-amyloid. The findings suggest that reducing RyanR2 activity may be a potential target for therapeutic intervention in AD.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Sarah Mustaly-Kalimi, Wacey Gallegos, Robert A. Marr, Alice Gilman-Sachs, Daniel A. Peterson, Israel Sekler, Grace E. Stutzmann
Summary: Impairments in Ca2+ signaling disrupt lysosomal acidification and contribute to pathological protein aggregation in neurodegenerative disorders like AD. Targeting the RyR-Ca2+ pathway could be a potential therapeutic intervention.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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)
Review
Cardiac & Cardiovascular Systems
Mary R. Sy, Joshua A. Keefe, Jeffrey P. Sutton, Xander H. T. Wehrens
Summary: Space medicine is crucial for human exploration of outer space and contributes to advancements in science, technology, and medicine. Astronauts and spaceflight participants face unique health challenges due to the harsh conditions in outer space, including microgravity and other hazards, particularly in relation to the heart. This review summarizes the existing literature on the effects of spaceflight on cardiac structure and function, as well as the impact of microgravity on cardiac calcium handling. The findings can inform future studies and therapies, and are also relevant to other physiological states resembling microgravity, such as prolonged horizontal bed rest and immobilization.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Kinya Seo, Yuta Yamamoto, Anna Kirillova, Masataka Kawana, Sunil Yadav, Yong Huang, Qianru Wang, Kerry V. Lane, Beth L. Pruitt, Marco V. Perez, Daniel Bernstein, Joseph C. Wu, Matthew T. Wheeler, Victoria N. Parikh, Euan A. Ashley
Summary: R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and improves cardiac output without lowering heart rate by dual blockade of alpha 1-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction.
Article
Cardiac & Cardiovascular Systems
Jinhong Wei, Wenting Guo, Ruiwu Wang, John Paul Estillore, Darrell Belke, Yong-Xiang Chen, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, S. R. Wayne Chen
Summary: The physiological significance of PKA phosphorylation of RyR2 in the heart is still poorly understood. Recent structural studies have shown that the PKA phosphorylation site S2030 in RyR2 is located within a pathway that is important for the termination of Ca2+ release. We investigated the impact of S2030 mutations on Ca2+ release termination in cells and generated a mouse model to study the role of S2030 in a physiological setting.
CIRCULATION RESEARCH
(2023)
Article
Neurosciences
Daisuke Sato, Hitoshi Uchinoumi, Donald M. Bers
Summary: Increasing SERCA activity has a dual effect on the propensity of arrhythmogenic Ca waves, promoting their generation at lower levels but potentially aborting them at higher levels. Factors influencing Ca wave propagation include diffusive coupling between Ca sparks, Ca buffers, intra-SR Ca diffusion, and distance between CRUs.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Physiology
Michael Fill, Dirk Gillespie
Summary: Research on diastolic SR Ca2+ leak and the impact of RyR array size on the leak shows that larger arrays produce larger and more frequent Ca2+ release events, and are more sensitive to small changes in dyadic Ca2+ buffer levels.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Review
Physiology
Almudena Val-Blasco, Marta Gil-Fernandez, Angelica Rueda, Laetitia Pereira, Carmen Delgado, Tarik Smani, Gema Ruiz Hurtado, Maria Fernandez-Velasco
Summary: This review summarizes key findings related to Ca2+ mishandling in heart failure (HF), highlighting the increasing focus on identifying new targets and their role in disease progression. Recent studies have identified potential targets in three major emerging areas involved in regulating Ca2+ handling, contributing to the understanding of HF progression.
Article
Endocrinology & Metabolism
Patrick A. Fletcher, Ben Thompson, Chante Liu, Richard Bertram, Leslie S. Satin, Arthur S. Sherman
Summary: The standard model for Ca2+ oscillations in insulin-secreting pancreatic 13 cells relies on voltage-activated Ca2+ channels for Ca2+ entry. These channels work together with ATP-dependent K+ channels to regulate the secretion of insulin in response to the metabolic state of the cells. However, an alternative model proposes that calcium-induced calcium release from the endoplasmic reticulum is the key driver of islet oscillations. This study shows that the alternative model is incompatible with established experimental data and that the standard model provides a better explanation for the new observations.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Sang Youn Hwang, Hongqun Liu, Samuel S. Lee
Summary: Cirrhotic cardiomyopathy is a syndrome characterized by weakened cardiac systolic and diastolic function in patients with cirrhosis. The calcium handling system, including calcium channels, intracellular calcium-regulatory apparatus, and pertinent proteins, plays a crucial role in the cardiac function in cirrhotic cardiomyopathy. Multiple defects in calcium handling contribute to the pathogenesis of cirrhotic cardiomyopathy, including the reduction of L-type calcium channels and calcium leakage in cirrhotic cardiomyocytes. The decreased calcium storage in the sarcoplasmic reticulum leads to decreased cardiac contractility.
Article
Immunology
Zhao Wang, Xi Zhao, Hongmei Zhou, Delu Che, Xiaojie Du, Dan Ye, Weihui Zeng, Songmei Geng
Summary: Mast cell activation is associated with the pathogenesis of various immune dysregulatory skin disorders. Recent studies have shown that the activation of an IgE-independent pseudo-allergic route is mainly mediated through Mas-Related G protein-coupled receptor X2 (MRGPRX2) and regulated by Ryanodine receptor (RYR). This finding provides insights into the role of RYR in MRGPRX2-mediated pseudo-allergic dermatitis.
FRONTIERS IN IMMUNOLOGY
(2023)
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)