Article
Biochemistry & Molecular Biology
Keisuke Hitachi, Yuri Kiyofuji, Hisateru Yamaguchi, Masashi Nakatani, Masafumi Inui, Kunihiro Tsuchida
Summary: This study investigated the effects of the loss of MyHC-IIb and MyHC-IIx on skeletal muscle function using a mouse model. The results showed that the simultaneous loss of IIb and IIx led to severe muscle hypoplasia after 2 weeks of age in mice. Increased expression of other MyHCs was observed in 3-week-old mice, but it was not sufficient to compensate for the loss of IIb and IIx. Aberrant sarcomere structure and altered expression of sarcomere components were also observed. These findings contribute to the understanding of molecular mechanisms underlying skeletal muscle wasting disorders caused by the loss of skeletal muscle MyHCs.
Article
Geriatrics & Gerontology
Dominika Krakova, Andrew M. Holwerda, Milan W. Betz, Kaleen M. Lavin, Marcas M. Bamman, Luc J. C. van Loon, Lex B. Verdijk, Tim Snijders
Summary: This study investigated the relationship between fiber type grouping and muscle mass and physical function. The results showed that there was no association between fiber type grouping and lower body strength or muscle mass in healthy, older men. Additionally, 12 weeks of resistance training resulted in specific hypertrophy of type II muscle fibers but did not affect fiber type grouping.
EXPERIMENTAL GERONTOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Gabryela Kuhnen, Tiago Guedes Russomanno, Marta Murgia, Nicolas J. Pillon, Martin Schoenfelder, Henning Wackerhage
Summary: Adult skeletal muscle fibres can be classified into different types based on the expression of specific genes. The proportions of these muscle fibre types can be altered through gene gain or loss-of-function. In particular, transcriptional regulators play a significant role in regulating the expression of muscle fibre-specific genes. After exercise, the expression of certain genes increases or decreases, suggesting their involvement in muscle fibre adaptation. DNA sequence variants of muscle fibre genes may contribute to the variation in muscle fibre type proportions in the human population.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Izumi Matsuba, Rikako Fujita, Kaoruko Iida
Summary: In this study, the effect of palmitic acid (PA), the most common fatty acid component in human fat, on muscle fiber type was assessed, focusing on the expression of fiber-type-specific myosin heavy chain (MHC). The study found that PA selectively suppresses the mRNA and protein expression of fast-twitch MHC, potentially providing a pathogenic mechanism for age-related sarcopenia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Giorgio Varesco, Cecile Coudy-Gandilhon, Thomas Lapole, Alice Decourt, Marine Gueugneau, Jean-Claude Barthelemy, Frederic Roche, Daniel Bechet, Leonard Feasson, Vianney Rozand
Summary: The study found that physical activity level was positively associated with the capacity of very old women to perform a fatiguing test, while the physical activity of very old men was not correlated with muscle performance. Increasing steps per day count could provide a sufficient stimulus for adaptations in less active very old women.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Physiology
Alex A. Olmos, Adam J. Sterczala, Mandy E. Parra, Hannah L. Dimmick, Jonathan D. Miller, Jake A. Deckert, Stephanie A. Sontag, Philip M. Gallagher, Andrew C. Fry, Trent J. Herda, Michael A. Trevino
Summary: This study compared motor unit recruitment and firing rate patterns between sexes during different contraction intensities and found that females had higher firing rates and electromyographic signal amplitude, likely due to higher type I myosin heavy chain (MHC) content in their muscles.
Article
Biochemistry & Molecular Biology
Shawna L. McMillin, Erin C. Stanley, Luke A. Weyrauch, Jeffrey J. Brault, Barbara B. Kahn, Carol A. Witczak
Summary: Denervation induces insulin resistance in skeletal muscle, with the soleus muscle showing sustained resistance and the EDL muscle showing enhanced insulin sensitivity due to increased GLUT4 protein levels. Insulin-stimulated glucose uptake was significantly altered in both muscles post-denervation, showcasing differential effects in oxidative and glycolytic muscle types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
Joseph Foon Yoong Hoh
Summary: The kinetics of myosin control the speed and power of muscle contraction. Mammalian skeletal muscles express twelve kinetically different myosin heavy chain (MyHC) genes, providing a wide range of muscle speeds to meet various functional demands. This review provides an overview of the historical and current views on how cell lineage, neural impulse patterns, and thyroid hormone influence MyHC gene expression in limb muscles during development and adult life, and the molecular mechanisms involved.
JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMS AND ENVIRONMENTAL PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Brent A. Momb, Gillian K. Szabo, Joshua P. Mogus, Stuart R. Chipkin, Laura N. Vandenberg, Mark S. Miller
Summary: Our study found that acute exposures to a pharmacological estrogen receptor agonist and androgen receptor antagonist caused significant shifts in skeletal muscle function in male mice, affecting specific tension, myofilament lattice stiffness, and myosin-actin cross-bridge kinetics, particularly in different myosin heavy chain fiber types. These effects were observed even without changes in reproductive organs or mammary gland morphology, suggesting the need for early countermeasures to maintain physical function under similar conditions.
Article
Immunology
Saori Yonebayashi, Kazuko Tajiri, Mari Hara, Hiromitsu Saito, Noboru Suzuki, Satoshi Sakai, Taizo Kimura, Akira Sato, Akiyo Sekimoto, Satoshi Fujita, Ryuji Okamoto, Robert J. Schwartz, Toshimichi Yoshida, Kyoko Imanaka-Yoshida
Summary: TNC is an extracellular matrix glycoprotein expressed during embryogenesis and up-regulated under pathological conditions. Overexpression of TNC is associated with poor clinical prognosis.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Geriatrics & Gerontology
David Martin, Kevin Nay, Francois Robin, Amelie Rebillard, Luz Orfila, Brice Martin, Patricia Leroyer, Pascal Guggenbuhl, Suzanne Dufresne, Philippe Noirez, Martine Ropert, Olivier Loreal, Frederic Derbre
Summary: This study investigates the impact of iron excess on skeletal muscle structure and metabolic adaptations. The results suggest that skeletal muscle can protect itself from the deleterious effects of iron overload under pathophysiological conditions.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Review
Peripheral Vascular Disease
Masaaki Ito, Ryuji Okamoto, Hiromasa Ito, Ye Zhe, Kaoru Dohi
Summary: Regulation of muscle contraction is essential in the cardiovascular system, with the interaction between myosin and actin filaments being a common mechanism. The phosphorylation of myosin regulatory light chain plays a crucial role in smooth muscle contraction, while in cardiac muscle, troponin C is the primary target protein for Ca2+ with RLC phosphorylation also modulating contraction. Recent advances have improved our understanding of the regulatory role of RLC phosphorylation in smooth and cardiac muscles.
HYPERTENSION RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Hiroyasu Sakai, Yuta Suzuki, Yu Miyauchi, Fumiaki Sato, Yusuke Ando, Risako Kon, Nobutomo Ikarashi, Yoshihiko Chiba, Junzo Kamei, Tomoo Hosoe
Summary: Cancer patients often experience muscle atrophy, which is worsened by the decreased muscle regenerative capacity. Cisplatin, a cancer chemotherapeutic agent, has been found to cause muscle atrophy. This study explored the effects of cisplatin on the differentiation of myoblasts into myotubes. The results showed that cisplatin suppresses myogenesis and inhibits the expression of Sparcl1, which promotes C2C12 cell differentiation during myogenesis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Nutrition & Dietetics
Hye-Jin Lee, Hui-Ji Choi, Sang-Ah Lee, Dong Hyuk Baek, Jong Beom Heo, Gyu Yong Song, Wonhwa Lee
Summary: Rare ginsenosides, specifically protopanaxatriol-type, can improve skeletal muscle atrophy by promoting myoblast differentiation and repair, and reducing the expression of muscle atrophy-related molecules.
Article
Chemistry, Multidisciplinary
Kemal Ardag Gunay, Tova L. Ceccato, Jason S. Silver, Kendra L. Bannister, Olivia J. Bednarski, Leslie A. Leinwand, Kristi S. Anseth
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2019)
Article
Biochemistry & Molecular Biology
Chloe A. Johnson, Jonathan Walklate, Marina Svicevic, Srboljub M. Mijailovich, Carlos Vera, Anastasia Karabina, Leslie A. Leinwand, Michael A. Geeves
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Cell Biology
Kristen K. Bjorkman, Martin G. Guess, Brooke C. Harrison, Michael M. Polmear, Angela K. Peter, Leslie A. Leinwand
JOURNAL OF CELL SCIENCE
(2020)
Article
Cardiac & Cardiovascular Systems
Tova L. Ceccato, Rachel B. Starbuck, Jessica K. Hall, Cierra J. Walker, Tobin E. Brown, Jason P. Killgore, Kristi S. Anseth, Leslie A. Leinwand
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2020)
Article
Cardiac & Cardiovascular Systems
Angela K. Peter, Cierra J. Walker, Tova Ceccato, Christa L. Trexler, Christopher D. Ozeroff, Kimberly R. Lugo, Amy R. Perry, Kristi S. Anseth, Leslie A. Leinwand
Summary: The study revealed that chronic beta-AR stimulation in male rat hearts leads to fibrosis, while female rat hearts do not undergo the same response. Additionally, male CFs are more prone to activation compared to female CFs, contributing to increased fibrosis in male rat hearts. The higher beta-AR expression and PKA activation in male CFs may be the underlying mechanism for this sex difference in fibrotic response.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Engineering, Biomedical
Cierra J. Walker, Claudia Crocini, Daniel Ramirez, Anouk R. Killaars, Joseph C. Grim, Brian A. Aguado, Kyle Clark, Mary A. Allen, Robin D. Dowell, Leslie A. Leinwand, Kristi S. Anseth
Summary: Increased extracellular stiffness activates fibroblasts, leading to the transformation of transiently activated fibroblasts into myofibroblasts with condensed chromatin. The condensed chromatin structure of myofibroblasts is associated with cytoskeletal stability, and nuclear mechanosensing plays a key role in driving distinct chromatin signatures in persistently activated fibroblasts.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Cardiac & Cardiovascular Systems
Lindsey A. Lee, Lindsey J. Broadwell, Massimo Buvoli, Leslie A. Leinwand
Summary: The majority of MYH7b RNA undergoes exon skipping and cannot be translated into functional myosin. Introns flanking the alternatively spliced exon may be retained, influencing MYH7b expression and other cardiac genes. Previous studies showing cardiac MYH7b protein expression were likely due to antibody cross-reactivity, and disease-associated variants may operate through alternately spliced RNA itself.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Correction
Engineering, Biomedical
Cierra J. Walker, Claudia Crocini, Daniel Ramirez, Anouk R. Killaars, Joseph C. Grim, Brian A. Aguado, Kyle Clark, Mary A. Allen, Robin D. Dowell, Leslie A. Leinwand, Kristi S. Anseth
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Cardiac & Cardiovascular Systems
Deanna L. Muehleman, Claudia Crocini, Alison R. Swearingen, Christopher D. Ozeroff, Leslie A. Leinwand
Summary: The pathways leading to regression of pathological cardiac hypertrophy are strongly dependent on the hypertrophic trigger and significantly modified by sex. Understanding these mechanisms and considering sex differences are crucial for developing effective therapies.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Physiology
Jason A. Magida, Yuxiao Tan, Christopher E. Wall, Brooke C. Harrison, Thomas G. Marr, Angela K. Peter, Cecilia A. Riquelme, Leslie A. Leinwand
Summary: The Burmese python exhibits adaptive metabolic responses after consuming large meals, including liver enlargement, fatty liver, hyperlipidemia, and insulin resistance. These responses are reversible and involve the activation of hepatic nuclear receptors induced by fatty acids and bile acids.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Sarah J. Lehman, Claudia Crocini, Leslie A. Leinwand
Summary: This review discusses therapeutic strategies targeting the cardiac sarcomere, focusing on small molecules that modulate myosin motor protein activity. Four small molecules have shown promise in the treatment of hypertrophic and dilated cardiomyopathy, and similar approaches are being developed for other components of the sarcomere.
NATURE REVIEWS CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Thomas G. Martin, Miranda A. Juarros, Leslie A. Leinwand
Summary: Left ventricular hypertrophy is a major risk factor for cardiovascular morbidity and mortality. Evidence from the past three decades suggests that reverse ventricular remodelling is possible with existing heart disease therapies, leading to improved cardiac function and long-term health outcomes.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Biology
Artur Meller, Jeffrey M. Lotthammer, Louis G. Smith, Borna Novak, Lindsey A. Lee, Catherine C. Kuhn, Lina Greenberg, Leslie A. Leinwand, Michael J. Greenberg, Gregory R. Bowman
Summary: The design of compounds that can discriminate between closely related target proteins remains a challenge in drug discovery. This study shows that the probability of pocket opening is an important determinant of the potency of the myosin inhibitor blebbistatin. By using Markov state models, it was found that the probability of pocket opening accurately identifies which isoforms are most sensitive to blebbistatin inhibition and predicts blebbistatin binding affinities.
Article
Biochemical Research Methods
Qizhong Liang, Ya-Chu Chan, Jutta Toscano, Kristen K. Bjorkman, Leslie A. Leinwand, Roy Parker, Eva S. Nozik, David J. Nesbitt, Jun Ye
Summary: Rapid testing is crucial in combating pandemics like COVID-19. We investigated breath detection of SARS-CoV-2 using cavity-enhanced direct frequency comb spectroscopy and found it to be an effective alternative, rapid, and non-invasive test for COVID-19. This technique also shows potential for optical diagnoses of various biological conditions.
JOURNAL OF BREATH RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Lindsey J. Broadwell, Michael J. Smallegan, Kevin M. Rigby, Jose S. Navarro-Arriola, Rusty L. Montgomery, John L. Rinn, Leslie A. Leinwand
Summary: MYH7b is an ancient gene in the myosin heavy chain family that has been repurposed by alternative splicing to produce a long noncoding RNA in the human heart, which affects cardiac myosin composition.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)