Article
Biochemistry & Molecular Biology
Sean R. Cleary, Xuan Fang, Ellen E. Cho, Marsha P. Pribadi, Jaroslava Seflova, Jordan R. Beach, Peter M. Kekenes-Huskey, Seth L. Robia
Summary: The ATP-dependent ion pump SERCA is important for cell signaling by sequestering Ca2+ in the endoplasmic reticulum. The micropeptides PLB and DWORF regulate SERCA activity in the heart, with PLB inhibiting SERCA and DWORF stimulating it. This study shows that PLB prefers low Ca2+ states of SERCA, while DWORF prefers high Ca2+ states. Changes in their binding during Ca2+ elevations contribute to the regulation of cardiac performance.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Rodrigo Aguayo-Ortiz, Jeffery Creech, Eric N. Jimenez-Vazquez, Guadalupe Guerrero-Serna, Nulang Wang, Andre Monteiro da Rocha, Todd J. Herron, L. Michel Espinoza-Fonseca
Summary: Membrane proteins are a significant part of the human proteome, offering potential therapeutic targets. Utilizing a combination of computational simulations and experimental methods, this study successfully activated the cardiac Ca2+ pump (SERCA2a) in human iPSC-derived cardiac cells, demonstrating the safety of directly targeting SERCA2a activation as a therapeutic approach. This novel multiscale platform streamlines the identification of drug-like candidates, accelerating the design of effective therapies targeting membrane protein domains.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Fabrice Gonnot, Laura Boulogne, Camille Brun, Maya Dia, Yves Gouriou, Gabriel Bidaux, Christophe Chouabe, Claire Crola Da Silva, Sylvie Ducreux, Bruno Pillot, Andrea Kaczmarczyk, Christelle Leon, Stephanie Chanon, Coralie Perret, Franck Sciandra, Tanushri Dargar, Vincent Gache, Fadi Farhat, Laurent Sebbag, Thomas Bochaton, Helene Thibault, Michel Ovize, Melanie Paillard, Ludovic Gomez
Summary: Despite advancements in cardioprotection, novel therapeutic approaches are still required to prevent ischemia-reperfusion injury in patients. This study reveals that phosphorylation of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2) at serine 663 is a clinical and pathophysiological event affecting cardiac function. Inhibition of serine 663 phosphorylation enhances SERCA2 activity, mitigates cell death, and counteracts cytosolic and mitochondrial Ca2+ overload. These findings enhance our understanding of excitation/contraction coupling in cardiomyocytes and highlight the therapeutic potential of SERCA2 modulation in acute myocardial infarction.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jessica L. Braun, Mia S. Geromella, Sophie I. Hamstra, Holt N. Messner, Val A. Fajardo
Summary: Microgravity exposure causes muscle weakness and atrophy, with differences observed in SERCA function and RONS protein adduction between soleus and TA muscles. The impairment in Ca2+ uptake in soleus muscles may be attributed to increased RONS production, while the enhancement in TA muscles could be due to a shift towards faster muscle fiber types without elevated protein nitration and nitrosylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cardiac & Cardiovascular Systems
Changwon Kho
Summary: Impaired myocardial Ca2+ cycling is a crucial factor in the development of heart failure, leading to changes in contractile function and structural remodeling of the heart. The regulation of sarcoplasmic reticulum Ca2+ storage and release in cardiomyocytes relies heavily on Ca2+ handling proteins like SERCA2a pump. However, reduced expression and activity of SERCA2a are key features of heart failure, resulting in a growing interest in therapeutic approaches targeting SERCA2a. This review provides an overview of the regulatory mechanisms of the SERCA2a pump and explores potential strategies for SERCA2a-targeted therapy in both preclinical and clinical studies.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biophysics
Roman Nikolaienko, Elisa Bovo, Samantha L. Yuen, Levy M. Treinen, Kaja Berg, Courtney C. Aldrich, David D. Thomas, Razvan L. Cornea, Aleksey V. Zima
Summary: Compound 1 enhances SERCA2a Ca2+-ATPase and Ca2+ transport, improves intracellular Ca2+ dynamics, and has potential therapeutic effects for heart failure.
BIOPHYSICAL JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Cathrine R. Carlson, Jan Magnus Aronsen, Anna Bergan-Dahl, Marie Christine Moutty, Marianne Lunde, Per Kristian Lunde, Hilde Jarstadmarken, Pimthanya Wanichawan, Laetitia Pereira, Terje R. S. Kolstad, Bjorn Dalhus, Hariharan Subramanian, Susanne Hille, Geir Christensen, Oliver J. Mueller, Viacheslav Nikolaev, Donald M. Bers, Ivar Sjaastad, Xin Shen, William E. Louch, Enno Klussmann, Ole M. Sejersted
Summary: This study demonstrates that AKAP18 delta anchors and regulates CaMKII activity at the sarcoplasmic reticulum, contributing to the regulation of cardiac contraction and relaxation.
CIRCULATION RESEARCH
(2022)
Article
Oncology
Zhidong Li, Jia Guo, Yunfei Bian, Mingsheng Zhang
Summary: The study found that IMD can protect cardiomyocytes against thapsigargin-induced apoptosis, at least partially by activating the protein kinase A/SERCA pathway.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Multidisciplinary Sciences
Shuai Wang, You Zhou, Yuanyuan Luo, Rongsheng Kan, Jingwen Chen, Haochen Xuan, Chaofan Wang, Junhong Chen, Tongda Xu, Dongye Li
Summary: Transverse-tubules (T-tubules) play a key role in excitation-contraction coupling in cardiomyocytes, and this study investigated how sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) regulates T-tubules during myocardial ischemia/reperfusion (I/R) to improve cardiac function. The results showed that calpain activation during I/R led to proteolytic cleavage of junctophilin-2 (JPH2), altering T-tubule network and contraction function in cardiomyocytes and in vivo cardiac functions. Through suppressing calpain activity and regulating [Ca2+](i), SERCA2a ameliorated cardiomyocyte T-tubule remodeling and improved cardiac function in myocardial I/R.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Mark A. Valentim, Aditya N. Brahmbhatt, A. Russell Tupling
Summary: This article discusses the release and transport of calcium ions in healthy muscle, and the impact of changes in calcium ion concentrations on signaling pathways. It also explores the relationship between calcium ion transport impairments and the pathogenesis of skeletal muscle myopathies and cardiomyopathies.
BIOSCIENCE REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Syeda Samara Baksh, Richard E. Pratt, Jose Gomez, Victor J. Dzau, Conrad P. Hodgkinson
Summary: miRNA-based cellular reprogramming can silence genes and change cell fate. In this study, three proteins, Cbx1, PurB, and Sp3, were identified as being downregulated during the reprogramming of fibroblasts into cardiomyocytes. Knockdown or ablation of these proteins led to induction of cardiomyocyte gene expression in fibroblasts and conversion into cardiomyocytes in vivo. These proteins also formed a complex and were necessary for nucleosome localization and modification. The findings suggest that Cbx1, PurB, and Sp3 actively repress lineage-specific genes to control cell fate.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Cedric Montigny, Dong Liang Huang, Veronica Beswick, Thomas Barbot, Christine Jaxel, Marc le Maire, Ji-Shen Zheng, Nadege Jamin
Summary: The study reveals the significant regulatory role of Sarcolipin on SERCA1a, affecting calcium and ATP binding and transport activity. Palmitoylation is not necessary for SLN's association with SERCA1a, but has a small but statistically significant effect on SERCA1a phosphorylation.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Shoko Sawano, Wataru Mizunoya
Summary: This review summarizes the history of muscle fiber type classification and various staining methods used. The development of experimental methods for detecting myosin heavy chain proteins and the improvement in immunostaining with monoclonal antibodies are discussed. The information presented in this review will guide researchers in selecting optimal staining methods for their experimental conditions and purposes.
HISTOLOGY AND HISTOPATHOLOGY
(2022)
Review
Physiology
Mohamad Nusier, Anureet K. Shah, Naranjan S. Dhalla
Summary: The sarcoplasmic reticulum (SR) in the heart plays a crucial role in regulating intracellular calcium levels and influencing cardiac contraction and relaxation. Composed of various proteins and phospholipids, the SR function is closely linked to cardiac performance and can be targeted for drug development in heart disease treatment.
PHYSIOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Oksana P. P. Gerzen, Veronika O. O. Votinova, Iulia K. K. Potoskueva, Alyona E. E. Tzybina, Larisa V. V. Nikitina
Summary: The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. This article summarizes the impact of these cations on myosin ATPase activity and EF-hand proteins, particularly toxic cations. The affinity to various divalent cations depends on certain proteins or their isoforms and can alter with amino acid substitution and post-translational modification. Cardiac EF-hand proteins and the myosin ATP-binding pocket are potential molecular targets for toxic cations, which could significantly alter the mechanical characteristics of the heart muscle at the molecular level.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)