Hindlimb unweighting induces changes in the p38MAPK contractile pathway of the rat abdominal aorta

2009 ◽  
Vol 107 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Scott Matthew Summers ◽  
Yuichiro Hayashi ◽  
Steven Vu Nguyen ◽  
Thu Minh Nguyen ◽  
Ralph Earl Purdy
Keyword(s):  
Abdominal Aorta ◽  
Thin Filament ◽  
Orthostatic Intolerance ◽  
Thick Filament ◽  
Mek Inhibitor ◽  
Response Curves ◽  
Thin Filament Regulation ◽  
Hindlimb Unweighting ◽  
Downstream Target ◽  
Sb 203580

Hindlimb unweighting (HLU) of rats is a model used to mimic the cephalic fluid shift potentially involved in the orthostatic intolerance experienced by astronauts. Certain arteries in these rats exhibit a decreased contractile response to adrenergic agonists. It was shown previously that this may be caused by changes in thick filament regulation (Summers et al., Vascul Pharmacol 48: 208–214, 2008). In the present study, it was hypothesized that HLU also modifies thin filament regulation by effects on p38MAPK and ERK. Abdominal aorta rings from 20-day HLU rats and untreated controls were subjected to phenylephrine and phorbol 12,13-dibutyrate (PDBU) concentration response curves in the presence and absence of two inhibitors: the p38MAPK inhibitor SB-203580 and the MEK inhibitor U-0126. SB-203580 decreased control sensitivity to both agonists, but HLU sensitivity was not significantly affected. U-0126, which blocks enzymes immediately upstream of ERK, affected sensitivity to both agonists equally between control and HLU. Western blot analysis revealed no change in total levels of p38MAPK and its downstream target heat shock protein 27 but did reveal a decrease in phosphorylated levels of both after stimulation with PDBU and phenylephrine after HLU treatment. Neither total ERK nor phosphorylated levels after stimulation were affected by HLU. Total levels of caldesmon, a molecule downstream of both pathways, were decreased, but phosphorylated levels after stimulation were decreased by roughly twice as much. The results of this study demonstrate that HLU downregulates p38MAPK, but not ERK, signaling. In turn, this may decrease actin availability for contraction.

scholarly journals Cardiac thin filament regulation and the Frank–Starling mechanism

2014 ◽  
Vol 64 (4) ◽  
pp. 221-232 ◽  
Author(s):  
Fuyu Kobirumaki-Shimozawa ◽  
Takahiro Inoue ◽  
Seine A. Shintani ◽  
Kotaro Oyama ◽  
Takako Terui ◽  
...  
Keyword(s):  
Thin Filament ◽  
Thin Filament Regulation

scholarly journals Spaceflight results in increase of thick filament but not thin filament proteins in the paramyosin mutant of Caenorhabditis elegans

2008 ◽  
Vol 41 (5) ◽  
pp. 816-823 ◽  
Author(s):  
R. Adachi ◽  
T. Takaya ◽  
K. Kuriyama ◽  
A. Higashibata ◽  
N. Ishioka ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Thin Filament ◽  
Thick Filament ◽  
Thin Filament Proteins

scholarly journals INTRINSIC BIREFRINGENCE OF GLYCERINATED MYOFIBRILS

1971 ◽  
Vol 51 (3) ◽  
pp. 763-771 ◽  
Author(s):  
Richard H. Colby
Keyword(s):  
Thin Filament ◽  
Striated Muscle ◽  
Thick Filament ◽  
Weight Basis ◽  
Macromolecular Structure ◽  
Form Birefringence ◽  
Sliding Filament Theory ◽  
Filament Protein ◽  
Formalin Fixed ◽  
Intrinsic Birefringence

Patterns of intrinsic birefringence were revealed in formalin-fixed, glycerinated myofibrils from rabbit striated muscle, by perfusing them with solvents of refractive index near to that of protein, about 1.570. The patterns differ substantially from those obtained in physiological salt solutions, due to the elimination of edge- and form birefringence. Analysis of myofibrils at various stages of shortening has produced results fully consistent with the sliding filament theory of contraction. On a weight basis, the intrinsic birefringence of thick-filament protein is about 2.4 times that of thin-filament protein. Nonadditivity of thick- and thin-filament birefringence in the overlap regions of A bands may indicate an alteration of macromolecular structure due to interaction between the two types of filaments.

scholarly journals Specific Myosin Heavy Chain Mutations Suppress Troponin I Defects in Drosophila Muscles

1999 ◽  
Vol 144 (5) ◽  
pp. 989-1000 ◽  
Author(s):  
William A. Kronert ◽  
Angel Acebes ◽  
Alberto Ferrús ◽  
Sanford I. Bernstein
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Thin Filament ◽  
Troponin I ◽  
Point Mutations ◽  
Thick Filament ◽  
Actin Binding ◽  
Filament Protein ◽  
Phenotypic Rescue

We show that specific mutations in the head of the thick filament molecule myosin heavy chain prevent a degenerative muscle syndrome resulting from the hdp2 mutation in the thin filament protein troponin I. One mutation deletes eight residues from the actin binding loop of myosin, while a second affects a residue at the base of this loop. Two other mutations affect amino acids near the site of nucleotide entry and exit in the motor domain. We document the degree of phenotypic rescue each suppressor permits and show that other point mutations in myosin, as well as null mutations, fail to suppress the hdp2 phenotype. We discuss mechanisms by which the hdp2 phenotypes are suppressed and conclude that the specific residues we identified in myosin are important in regulating thick and thin filament interactions. This in vivo approach to dissecting the contractile cycle defines novel molecular processes that may be difficult to uncover by biochemical and structural analysis. Our study illustrates how expression of genetic defects are dependent upon genetic background, and therefore could have implications for understanding gene interactions in human disease.

scholarly journals Myosin-18B Regulates Higher-Order Organization of the Cardiac Sarcomere through Thin Filament Cross-Linking and Thick Filament Dynamics

Cell Reports ◽  
2020 ◽  
Vol 32 (9) ◽  
pp. 108090
Author(s):  
Sharissa L. Latham ◽  
Nadine Weiß ◽  
Kristin Schwanke ◽  
Claudia Thiel ◽  
David R. Croucher ◽  
...  
Keyword(s):  
Thin Filament ◽  
Thick Filament ◽  
Higher Order ◽  
Cross Linking ◽  
Cardiac Sarcomere ◽  
Filament Dynamics

scholarly journals Thin Filament Regulation of Relaxation in 3D Multi-Sarcomere Geometry

2009 ◽  
Vol 96 (3) ◽  
pp. 201a ◽  
Author(s):  
Srboljub M. Mijailovich ◽  
Oliver Kayser-Herald ◽  
Richard L. Moss ◽  
Michael A. Geeves
Keyword(s):  
Thin Filament ◽  
Thin Filament Regulation

Irradiations of rabbit myofibrils with an ultraviolet microbeam. I. Effects of ultraviolet light on the myofibril components necessary for contraction

1987 ◽  
Vol 65 (4) ◽  
pp. 363-375 ◽  
Author(s):  
Paula Wilson ◽  
Arthur Forer
Keyword(s):  
Ultraviolet Light ◽  
Dose Response ◽  
Thin Filament ◽  
Primary Effect ◽  
Chromosome Movement ◽  
Response Curves ◽  
Rabbit Psoas ◽  
Ultraviolet Microbeam ◽  
Filament Structure ◽  
Wavelength Light

Glycerinated rabbit psoas myofibrils, F-actin, and myofibril ghosts were irradiated with ultraviolet light (UV) to investigate how UV blocks myofibril contraction. Myofibril contraction is most sensitive to 270- and 290-nm wavelength light. We irradiated I and A bands separately with 270- and 290-nm wavelength light using a UV microbeam and constructed dose-response curves for blocking sarcomere contraction. For both wavelengths, irradiations of A bands required less energy per area to block contraction than did irradiations of I bands, suggesting that the primary effects of both 270- and 290-nm wavelength light in stopping myofibril contraction are on myosin. We investigated whether the primary effect of UV in blocking I-band contraction is the depolymerization of actin by comparing the relative sensitivities of I-band contraction, F-actin depolymerization, and thin filament depolymerization to 270- and 290-nm light. We also compared the dose of UV required to depolymerize F-actin in solution with the dose needed to block I-band contraction and the dose required to alter thin filament structure in myofibril ghosts. The results confirm that UV blocks I-band contraction by depolymerizing actin. We discuss how the results might be relevant to the hypothesis that an actomyosin-based system is involved in chromosome movement.

scholarly journals I-Band Titin in Cardiac Muscle Is a Three-Element Molecular Spring and Is Critical for Maintaining Thin Filament Structure

1999 ◽  
Vol 146 (3) ◽  
pp. 631-644 ◽  
Author(s):  
Wolfgang A. Linke ◽  
Diane E. Rudy ◽  
Thomas Centner ◽  
Mathias Gautel ◽  
Christian Witt ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Thin Filament ◽  
Thick Filament ◽  
Cardiac Cells ◽  
Elastic Behavior ◽  
Unique Region ◽  
Cardiac Titin ◽  
Filament Structure ◽  
Pevk Domain ◽  
Cardiac Sarcomeres

In cardiac muscle, the giant protein titin exists in different length isoforms expressed in the molecule's I-band region. Both isoforms, termed N2-A and N2-B, comprise stretches of Ig-like modules separated by the PEVK domain. Central I-band titin also contains isoform-specific Ig-motifs and nonmodular sequences, notably a longer insertion in N2-B. We investigated the elastic behavior of the I-band isoforms by using single-myofibril mechanics, immunofluorescence microscopy, and immunoelectron microscopy of rabbit cardiac sarcomeres stained with sequence-assigned antibodies. Moreover, we overexpressed constructs from the N2-B region in chick cardiac cells to search for possible structural properties of this cardiac-specific segment. We found that cardiac titin contains three distinct elastic elements: poly-Ig regions, the PEVK domain, and the N2-B sequence insertion, which extends ∼60 nm at high physiological stretch. Recruitment of all three elements allows cardiac titin to extend fully reversibly at physiological sarcomere lengths, without the need to unfold Ig domains. Overexpressing the entire N2-B region or its NH2 terminus in cardiac myocytes greatly disrupted thin filament, but not thick filament structure. Our results strongly suggest that the NH2-terminal N2-B domains are necessary to stabilize thin filament integrity. N2-B–titin emerges as a unique region critical for both reversible extensibility and structural maintenance of cardiac myofibrils.

A Dominant Role of Cardiac Molecular Motors in the Intrinsic Regulation of Ventricular Ejection and Relaxation

Physiology ◽  
2007 ◽  
Vol 22 (2) ◽  
pp. 73-80 ◽  
Author(s):  
Aaron C. Hinken ◽  
R. John Solaro
Keyword(s):  
Molecular Motors ◽  
Thin Filament ◽  
Dominant Role ◽  
Thick Filament ◽  
Ejection Time ◽  
Filament Activation ◽  
Intrinsic Regulation ◽  
Myosin Interaction ◽  
Isovolumic Relaxation

Molecular motors housed in myosins of the thick filament react with thin-filament actins and promote force and shortening in the sarcomeres. However, other actions of these motors sustain sarcomeric activation by cooperative feedback mechanisms in which the actin-myosin interaction promotes thin-filament activation. Mechanical feedback also affects the actin-myosin interaction. We discuss current concepts of how these relatively under-appreciated actions of molecular motors are responsible for modulation of the ejection time and isovolumic relaxation in the beating heart.

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