keyword
https://read.qxmd.com/read/38464089/human-calpain-3-and-its-structural-plasticity-dissociation-of-a-homohexamer-into-dimers-on-binding-titin
#21
Qilu Ye, Amy Henrickson, Borries Demeler, Vitor Hugo Balasco Serrão, Peter L Davies
Calpain-3 is an intracellular Ca 2+ -dependent cysteine protease abundant in skeletal muscle. Its physiological role in the sarcomere is thought to include removing damaged muscle proteins after exercise. Loss-of-function mutations in its single-copy gene cause a dystrophy of the limb-girdle muscles. These mutations, of which there are over 500 in humans, are spread all along this 94-kDa multi-domain protein that includes three 40+-residue sequences (NS, IS1, and IS2). The latter sequences are unique to this calpain isoform and are hypersensitive to proteolysis...
March 3, 2024: bioRxiv
https://read.qxmd.com/read/38462126/translating-myosin-binding-protein-c-and-titin-abnormalities-to-whole-heart-function-using-a-novel-calcium-contraction-coupling-model
#22
JOURNAL ARTICLE
Theo Arts, Aurore Lyon, Tammo Delhaas, Diederik W D Kuster, Jolanda van der Velden, Joost Lumens
Mutations in cardiac myosin-binding protein C (cMyBP-C) or titin may respectively lead to hypertrophic (HCM) or dilated (DCM) cardiomyopathies. The mechanisms leading to these phenotypes remain unclear because of the challenge of translating cellular abnormalities to whole-heart and system function. We developed and validated a novel computer model of calcium-contraction coupling incorporating the role of cMyBP-C and titin based on the key assumptions: 1) tension in the thick filament promotes cross-bridge attachment mechanochemically, 2) with increasing titin tension, more myosin heads are unlocked for attachment, and 3) cMyBP-C suppresses cross-bridge attachment...
March 8, 2024: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/38456261/why-ancestral-diversity-in-genetic-testing-matters-lessons-learned-from-hypertrophic-cardiomyopathy
#23
EDITORIAL
Kyla E Dunn
No abstract text is available yet for this article.
March 8, 2024: Circulation. Heart Failure
https://read.qxmd.com/read/38451233/mechanisms-of-myosin-ii-force-generation-insights-from-novel-experimental-techniques-and-approaches
#24
REVIEW
Dilson E Rassier, Alf Månsson
Myosin II is a molecular motor that converts chemical energy derived from ATP hydrolysis into mechanical work. Myosin II isoforms are responsible for muscle contraction and a range of cell functions relying on the development of force and motion. When the motor attaches to actin, ATP is hydrolyzed, and inorganic phosphate (Pi ) and ADP are released from its active site. These reactions are coordinated with changes in the structure of myosin, promoting the so called "power-stroke" that causes sliding of actin filaments...
March 7, 2024: Physiological Reviews
https://read.qxmd.com/read/38447917/the-diagnostic-and-therapeutic-implications-of-phenocopies-and-mimics-of-hypertrophic-cardiomyopathy
#25
REVIEW
Athanasios Bakalakos, Emanuele Monda, Perry Mark Elliott
Hypertrophic cardiomyopathy (HCM) is a common myocardial disease defined by increased left ventricular wall thickness unexplained by loading conditions. It is frequently caused by pathogenic variants in sarcomeric protein genes, but several other syndromic, metabolic, infiltrative, and neuromuscular diseases can result in HCM phenocopies. This review summarizes the current understanding of these HCM mimics, highlighting their importance across the life course. The central role of a comprehensive, multiparametric diagnostic approach and the potential of precision medicine in tailoring treatment strategies are emphasized...
March 4, 2024: Canadian Journal of Cardiology
https://read.qxmd.com/read/38446619/the-rhogap-rrc-1-is-required-for-the-assembly-or-stability-of-integrin-adhesion-complexes-and-is-a-member-of-the-pix-pathway-in-muscle
#26
JOURNAL ARTICLE
Jasmine C Moody, Hiroshi Qadota, Guy M Benian
GTPases cycle between active GTP bound and inactive GDP bound forms. Exchange of GDP for GTP is catalyzed by guanine nucleotide exchange factors (GEFs). GTPase activating proteins (GAPs) accelerate GTP hydrolysis, to promote the GDP bound form. We reported that the RacGEF, PIX-1, is required for assembly of integrin adhesion complexes (IAC) in striated muscle of C. elegans . In C. elegans , IACs are found at the muscle cell boundaries (MCBs), and bases of sarcomeric M-lines and dense bodies (Z-disks). Screening C...
March 6, 2024: Molecular Biology of the Cell
https://read.qxmd.com/read/38438525/exploring-ttn-variants-as-genetic-insights-into-cardiomyopathy-pathogenesis-and-potential-emerging-clues-to-molecular-mechanisms-in-cardiomyopathies
#27
JOURNAL ARTICLE
Amir Ghaffari Jolfayi, Erfan Kohansal, Serwa Ghasemi, Niloofar Naderi, Mahshid Hesami, MohammadHossein MozafaryBazargany, Maryam Hosseini Moghadam, Amir Farjam Fazelifar, Majid Maleki, Samira Kalayinia
The giant protein titin (TTN) is a sarcomeric protein that forms the myofibrillar backbone for the components of the contractile machinery which plays a crucial role in muscle disorders and cardiomyopathies. Diagnosing TTN pathogenic variants has important implications for patient management and genetic counseling. Genetic testing for TTN variants can help identify individuals at risk for developing cardiomyopathies, allowing for early intervention and personalized treatment strategies. Furthermore, identifying TTN variants can inform prognosis and guide therapeutic decisions...
March 4, 2024: Scientific Reports
https://read.qxmd.com/read/38436290/food-grade-titanium-dioxide-e171-and-zinc-oxide-nanoparticles-induce-mitochondrial-permeability-and-cardiac-damage-after-oral-exposure-in-rats
#28
JOURNAL ARTICLE
Francisco Correa Segura, Fernanda Isabel Macías Macías, Kimberly Abigaíl Velázquez Delgado, María Del Pilar Ramos-Godinez, Angélica Ruiz-Ramírez, Pedro Flores, Elizabeth Huerta-García, Rebeca López-Marure
Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are found in diverse products for human use. E171 is used as whitening agent in food and cosmetics, and ZnO NPs in food packaging. Their potential multi-organ toxicity has raised concerns on their safety. Since mitochondrial dysfunction is a key aspect of cardio-pathologies, here, we evaluate the effect of chronic exposure to E171 and ZnO NPs in rats on cardiac mitochondria. Changes in cardiac electrophysiology and body weight were measured...
March 4, 2024: Nanotoxicology
https://read.qxmd.com/read/38436094/impairment-of-the-adrenergic-reserve-associated-with-exercise-intolerance-in-a-murine-model-of-heart-failure-with-preserved-ejection-fraction
#29
JOURNAL ARTICLE
Lukas Semmler, Tobias Jeising, Judith Huettemeister, Marc Bathe-Peters, Konstantina Georgoula, Rashin Roshanbin, Paulina Sander, Shu Fu, David Bode, Felix Hohendanner, Burkert Pieske, Paolo Annibale, Gabriele G Schiattarella, Christian U Oeing, Frank R Heinzel
AIM: Exercise intolerance is the central symptom in patients with heart failure with preserved ejection fraction. In the present study, we investigated the adrenergic reserve both in vivo and in cardiomyocytes of a murine cardiometabolic HFpEF model. METHODS: 12-week-old male C57BL/6J mice were fed regular chow (control) or a high-fat diet and L-NAME (HFpEF) for 15 weeks. At 27 weeks, we performed (stress) echocardiography and exercise testing and measured the adrenergic reserve and its modulation by nitric oxide and reactive oxygen species in left ventricular cardiomyocytes...
March 4, 2024: Acta Physiologica
https://read.qxmd.com/read/38429930/reorganization-of-mitochondria-organelle-interactions-during-postnatal-development-in-skeletal-muscle
#30
JOURNAL ARTICLE
Yuho Kim, Hailey A Parry, T Bradley Willingham, Greg Alspaugh, Eric Lindberg, Christian A Combs, Jay R Knutson, Christopher K E Bleck, Brian Glancy
Skeletal muscle cellular development requires the integrated assembly of mitochondria and other organelles adjacent to the sarcomere in support of muscle contractile performance. However, it remains unclear how interactions among organelles and with the sarcomere relates to the development of muscle cell function. Here, we combine 3D volume electron microscopy, proteomic analyses, and live cell functional imaging to investigate the postnatal reorganization of mitochondria-organelle interactions in skeletal muscle...
March 1, 2024: Journal of Physiology
https://read.qxmd.com/read/38422589/number-of-denatured-rigor-cross-bridges-determines-the-intracellular-volume-shrinkage-in-porcine-muscle-fibre-under-pse-inducing-condition
#31
JOURNAL ARTICLE
Cong Yin, Siyang Wu, Nan Yang, Tingyang Ai, Jiawei Wan, Qin Rui, Hong Liu, Hairong Xiong, Jiao Liu
Earlier onset of rigor mortis is a critical physiological progress occurring in the development of pale soft and exudative (PSE) meat. However, how rigor cross-bridges denature under different physiological conditions and their impacts on water-holding capacity remains unclear. To address this scientific question, we firstly established a method to quantify the extent of rigor cross-bridge denaturation using skinned fibres prepared from porcine longissimus thoracis et lumborum muscle. Effects of pH and temperature on the kinetics of rigor cross-bridge denaturation, actomyosin denaturation and shrinkage of muscle fibre were studied...
February 27, 2024: Meat Science
https://read.qxmd.com/read/38422011/native-top-down-mass-spectrometry-for-characterizing-sarcomeric-proteins-directly-from-cardiac-tissue-lysate
#32
JOURNAL ARTICLE
Emily A Chapman, Brad H Li, Boris Krichel, Hsin-Ju Chan, Kevin M Buck, David S Roberts, Ying Ge
Native top-down mass spectrometry (nTDMS) has emerged as a powerful structural biology tool that can localize post-translational modifications (PTMs), explore ligand-binding interactions, and elucidate the three-dimensional structure of proteins and protein complexes in the gas-phase. Fourier-transform ion cyclotron resonance (FTICR) MS offers distinct capabilities for nTDMS, owing to its ultrahigh resolving power, mass accuracy, and robust fragmentation techniques. Previous nTDMS studies using FTICR have mainly been applied to overexpressed recombinant proteins and protein complexes...
February 29, 2024: Journal of the American Society for Mass Spectrometry
https://read.qxmd.com/read/38419621/targeted-brain-specific-tauopathy-compromises-peripheral-skeletal-muscle-integrity-and-function
#33
JOURNAL ARTICLE
Bryan Alava, Gabriela Hery, Silvana Sidhom, Miguel Gutierrez-Monreal, Stefan Prokop, Karyn A Esser, Jose Abisambra
Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8)...
2024: Aging brain
https://read.qxmd.com/read/38412038/allelic-heterogeneity-of-ttntv-cardiomyopathy-can-be-modeled-in-adult-zebrafish
#34
JOURNAL ARTICLE
Ping Zhu, Jiarong Li, Feixiang Yan, Shahidul Islam, Xueying Lin, Xiaolei Xu
Allelic heterogeneity (AH) has been noted in truncational TTN (TTNtv)-associated dilated cardiomyopathy (DCM), i.e., mutations affecting A-band-encoding exons are pathogenic, but those affecting Z-disc-encoding exons are likely benign. The lack of an in vivo animal model that recapitulates AH hinders the deciphering of the underlying mechanism. Here, we explored zebrafish as a candidate vertebrate model by phenotyping a collection of zebrafish ttntv alleles. We noted that cardiac function and sarcomere structure are more severely disrupted in ttntv-A than in ttntv-Z homozygous embryos...
February 27, 2024: JCI Insight
https://read.qxmd.com/read/38406555/hypertrophic-cardiomyopathy-in-mybpc3-carriers-in-aging
#35
JOURNAL ARTICLE
Kalyani Ananthamohan, Julian E Stelzer, Sakthivel Sadayappan
Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the myocardium, leading to arrhythmias, heart failure, and elevated risk of sudden cardiac death, particularly among the young. This inherited disease is predominantly caused by mutations in sarcomeric genes, among which those in the cardiac myosin binding protein-C3 ( MYBPC3 ) gene are major contributors. HCM associated with MYBPC3 mutations usually presents in the elderly and ranges from asymptomatic to symptomatic forms, affecting numerous cardiac functions and presenting significant health risks with a spectrum of clinical manifestations...
January 2024: The journal of cardiovascular aging
https://read.qxmd.com/read/38397924/the-flnc-ala1186val-variant-linked-to-cytoplasmic-body-myopathy-and-cardiomyopathy-causes-protein-instability
#36
JOURNAL ARTICLE
Marion Onnée, Audrey Bénézit, Sultan Bastu, Aleksandra Nadaj-Pakleza, Béatrice Lannes, Flavie Ader, Corinne Thèze, Pascal Cintas, Claude Cances, Robert-Yves Carlier, Corinne Metay, Mireille Cossée, Edoardo Malfatti
Filamin C-related disorders include myopathies and cardiomyopathies linked to variants in the FLNC gene. Filamin C belongs to a family of actin-binding proteins involved in sarcomere stability. This study investigates the pathogenic impact of the FLNC c.3557C > T (p.Ala1186Val) pathogenic variant associated with an early-onset cytoplasmic body myopathy and cardiomyopathy in three unrelated patients. We performed clinical imaging and myopathologic and genetic characterization of three patients with an early-onset myopathy and cardiomyopathy...
January 30, 2024: Biomedicines
https://read.qxmd.com/read/38392255/phospholamban-p-leu39-cardiomyopathy-compared-with-other-sarcomeric-cardiomyopathies-age-matched-patient-cohorts-and-literature-review
#37
JOURNAL ARTICLE
Andreea Sorina Afana, Laura Vasiliu, Radu Sascău, Robert Daniel Adam, Cristina Rădulescu, Sebastian Onciul, Eliza Cinteză, Adela Chirita-Emandi, Ruxandra Jurcuț
Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4...
January 28, 2024: Journal of Cardiovascular Development and Disease
https://read.qxmd.com/read/38391059/metastasis-associated-1-localizes-to-the-sarcomeric-z-disc-and-is-implicated-in-skeletal-muscle-pathology
#38
JOURNAL ARTICLE
Hongsheng Xue, Li Han, Haidi Sun, Zhe Piao, Wenjun Cao, Haili Qian, Zhilong Zhao, Ming-Fei Lang, Chundong Gu
Metastasis-associated 1 (MTA1), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) corepressor complex, was reported to be expressed in the cytoplasm of skeletal muscles. However, the exact subcellular localization and the functional implications of MTA1 in skeletal muscles have not been examined. This study aims to demonstrate the subcellular localization of MTA1 in skeletal muscles and reveal its possible roles in skeletal muscle pathogenesis. Striated muscles (skeletal and cardiac) from C57BL/6 mice of 4-5 weeks were collected to examine the expression of MTA1 by Western blotting and immunohistochemistry...
February 23, 2024: Cytoskeleton
https://read.qxmd.com/read/38389574/a-myh7-variant-in-a-five-generation-family-with-hypertrophic-cardiomyopathy
#39
JOURNAL ARTICLE
Magda Franke, Tomasz Marcin Książczyk, Marta Dux, Przemysław Chmielewski, Grażyna Truszkowska, Dorota Czapczak, Radosław Pietrzak, Zofia Teresa Bilinska, Urszula Demkow, Bożena Werner
Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500-1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. MYH7 gene encoding a myosin heavy chain beta, together with MYPBC3 gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of MYH7 responsible for HCM in a five-generation family with a history of cardiac problems. Methods: The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance...
2024: Frontiers in Genetics
https://read.qxmd.com/read/38386705/structure-of-mavacamten-free-human-cardiac-thick-filaments-within-the-sarcomere-by-cryoelectron-tomography
#40
JOURNAL ARTICLE
Liang Chen, Jun Liu, Hosna Rastegarpouyani, Paul M L Janssen, Jose R Pinto, Kenneth A Taylor
Heart muscle has the unique property that it can never rest; all cardiomyocytes contract with each heartbeat which requires a complex control mechanism to regulate cardiac output to physiological requirements. Changes in calcium concentration regulate the thin filament activation. A separate but linked mechanism regulates the thick filament activation, which frees sufficient myosin heads to bind the thin filament, thereby producing the required force. Thick filaments contain additional nonmyosin proteins, myosin-binding protein C and titin, the latter being the protein that transmits applied tension to the thick filament...
February 27, 2024: Proceedings of the National Academy of Sciences of the United States of America
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