Microtubule mechanics in the working myocyte

Robison, Patrick; Prosser, Benjamin L.

doi:10.1113/jp273046

Cited by 26 publications

(25 citation statements)

References 47 publications

(54 reference statements)

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“…Control cardiac myocytes (Fig. 1A, left) displayed a sparse, complex network of microtubules, similar to previous reports (Robison and Prosser, 2017). In contrast, cardiac myocytes treated with 100 μM H 2 O 2 (Fig.…”

Section: Oxidative Stress Increases Longitudinal Alignment Of the Micsupporting

confidence: 88%

Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice

Goldblum

McClellan

Hou

et al. 2020

Preprint

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AbstractIn the failing heart, the cardiac myocyte microtubule network is remodeled, which increases cellular stiffness and disrupts contractility, contributing to heart failure and death. However, the origins of this deleterious cytoskeletal reorganization are unknown. We now find that oxidative stress, a condition characteristic of failing heart cells, leads to cysteine oxidation of microtubules. Further, our electron and fluorescence microscopy experiments revealed regions of structural damage within the oxidized microtubule lattice. These damaged regions led to the lengthening, realignment, and acetylation of dynamic microtubules within cardiac myocytes. Thus, we found that oxidative stress acts inside of cardiac myocytes to facilitate a dramatic, pathogenic shift from a dynamic, multifaceted microtubule network into a highly acetylated, longitudinally aligned, and static microtubule network. Our results demonstrate how a disease condition characterized by oxidative stress can trigger a molecular oxidation event, which propagates a toxic cellular-scale transformation of the cardiac myocyte microtubule network.

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Section: Oxidative Stress Increases Longitudinal Alignment Of the Micsupporting

confidence: 88%

Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice

Goldblum

McClellan

Hou

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Although poorly understood in fish, the steps of myogenesis in mouse models provide clues, including commitment of muscle precursors, myoblast proliferation, migration, alignment, and fusion into myotubes (Buckingham and Rigby, 2014). Myocytes are mainly filled with myofibrils, which are long protein cords composed of myofilaments comprising molecules called myosin, actin, or titin (Sanger et al, 2016;Robison and Prosser, 2017). The relative contribution of hyperplasia and hypertrophy to muscle growth is known to be regulated by many nutritional factors, among which, proteins play a major role, given the importance of protein deposition on muscle growth (Alami-Durante et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Feeding Faba Beans (Vicia faba L.) Reduces Myocyte Metabolic Activity in Grass Carp (Ctenopharyngodon idellus)

Tian

et al. 2020

Front. Physiol.

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In this study, we aimed to explore the effects of faba bean (Vicia faba L.) on the energy metabolism of grass carp (Ctenopharyngodon idellus). A total of 180 fish (∼2900 g) were randomly assigned to six tanks (2.5 × 2.5 × 1.2 m; 30 individuals per tank) and fed either faba bean (Vicia faba L.) or a commercial diet for 120 days (3% body weight, twice per day). The results showed that faba bean-fed grass carp (FBFG) had significantly lower growth and higher fat accumulation in the mesenteric adipose tissue and hepatopancreas than commercial diet-fed grass carp (CDFG). Compared with CDFG, FBFG exhibited no significant difference in proximate composition of the muscle; however, an obvious decrease in muscle fiber size and significantly higher hardness, chewiness, and gumminess were observed. Transcriptome results showed that a total of 197 genes were differentially regulated in the dorsal muscle. Down-regulated genes included four genes annotated with myocyte development and 12 transcripts annotated with components of myofibrils. In addition, the FBFG group exhibited significantly lower expression of genes associated with oxygen transport, the mitochondrial respiratory chain, and creatine metabolism, suggesting reduced energy availability in the muscle of the FBFG. Moreover, using western-blotting and enzyme assays, we found decreased protein levels in the mitochondrial electron transport respiratory chain and creatine metabolism activities, as well as increased expression of autophagy marker protein levels, in the muscle of FBFG. Overall, our results suggest that an abnormal energy distribution may exist in grass carps after feeding with faba bean, which is reflected by a mass of fat deposition in the adipose tissue and hepatopancreas and subdued metabolic activity in the muscle.

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“…Together, the polymerized form of α-tubulin and β-tubulin assembles the microtubule network, which supports the architecture, contractile function and transportation of cytoplasmic constitutes within the cardiomyocyte [31][32][33]. Previously, we showed that tachypacing induces disruption of the microtubule network via activation of HDAC6, resulting in deacetylation, depolymerization and finally degradation of the depolymerized α-tubulin by calpain.…”

Section: Gga*-59 Post-treatment Restores α-Tubulin Networkmentioning

confidence: 57%

Heat shock protein inducer GGA*-59 reverses contractile and structural remodeling via restoration of the microtubule network in experimental Atrial Fibrillation

Marion

et al. 2019

Journal of Molecular and Cellular Cardiology

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Background: Atrial Fibrillation (AF) is the most common progressive tachyarrhythmia. AF progression is driven by abnormalities in electrical impulse formation and contractile function due to structural remodeling of cardiac tissue. Previous reports indicate that structural remodeling is rooted in derailment of protein homeostasis (proteostasis). Heat shock proteins (HSPs) play a critical role in facilitating proteostasis. Hence, the HSP-inducing compound geranylgeranylacetone (GGA) and its derivatives protect against proteostasis derailment in experimental models for AF. Whether these compounds also accelerate reversibility from structural remodeling in tachypaced cardiomyocytes is unknown. Objective: To investigate whether the potent HSP inducer GGA*-59 restores structural remodeling and contractile dysfunction in tachypaced cardiomyocytes and explore the underlying mechanisms. Materials and results: HL-1 cardiomyocytes post-treated with GGA*-59 or recombinant HSPB1 (rcHSPB1) revealed increased levels of HSPB1 expression and accelerated recovery from tachypacing (TP)-induced calcium transient (CaT) loss compared to non-treated cardiomyocytes. In addition, protein levels of the microtubule protein (acetylated) α-tubulin, and contractile proteins cardiac troponin I (cTnI) and troponin T (cTnT) were reduced after TP and significantly recovered by GGA*-59 or rcHSPB1 post-treatment. The mRNA levels of αtubulin encoding genes, but not cardiac troponin genes, were reduced upon TP and during recovery, but significantly enhanced by GGA*-59 and rcHSPB1 post-treatment. In addition, TP increased calpain activity, which remained increased during recovery and GGA*-59 post-treatment. However, HDAC6 activity, which deacetylates α-tubulin resulting in microtubule disruption, was significantly increased after TP and during recovery, but normalized to control levels by GGA*-59 or rcHSPB1 post-treatment in HL-1 cardiomyocytes. Conclusions: Our results imply that the HSP inducer GGA*-59 and recombinant HSPB1 accelerate recovery from TP-induced structural remodeling and contractile dysfunction in HL-1 cardiomyocytes. GGA*-59 increases HSPB1 levels, represses HDAC6 activity and restores contractile protein and microtubule levels after TP, indicating that HSP-induction is an interesting target to accelerate recovery from AF-induced remodeling.

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Microtubule mechanics in the working myocyte

Cited by 26 publications

References 47 publications

Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice

Oxidative stress pathogenically remodels the cardiac myocyte cytoskeleton via structural alterations to the microtubule lattice

Feeding Faba Beans (Vicia faba L.) Reduces Myocyte Metabolic Activity in Grass Carp (Ctenopharyngodon idellus)

Heat shock protein inducer GGA*-59 reverses contractile and structural remodeling via restoration of the microtubule network in experimental Atrial Fibrillation

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