Differential effects of ovariectomy on calcium activation of cardiac and soleus myofilaments

1999 ◽  
Vol 277 (2) ◽  
pp. H467-H473 ◽  
Author(s):  
Jonggonnee Wattanapermpool ◽  
Peter J. Reiser
Keyword(s):  
Thin Filament ◽  
Troponin I ◽  
Left Ventricular ◽  
Hormone Deficiency ◽  
Ovariectomized Rats ◽  
Maximal Tension ◽  
Cardiac Myofilament ◽  
Myofilament Activation ◽  
Thin Filament Proteins ◽  
Ventricular Trabeculae

The hypothesis that ovarian sex hormone deficiency affects cardiac myofilament activation was tested. Chemically skinned ventricular trabeculae and single soleus muscle fibers were prepared from 10- and 14-wk ovariectomized and control rats. Tension-pCa (−log [Ca2+]) relations of left ventricular trabeculae and soleus fibers were compared to test whether thin filament proteins are potential sites of modulated activation. Trabeculae from ovariectomized rats exhibited a significant increase in Ca2+ sensitivity with no change in maximal tension-generating ability. In contrast, soleus fibers demonstrated no shift in Ca2+ sensitivity but generated significantly less maximal tension. No changes in thin filament protein isoform expression or loss of thin filament proteins were apparent in the trabeculae or soleus fibers from ovariectomized rats. Although not directly tested, our results are consistent with a possible modulation of regulatory proteins (e.g., cardiac troponin I) to account for the observed change in myofilament responsiveness of hearts from ovariectomized rats. Other possible mechanisms for the altered myocardial Ca2+ sensitivity after ovariectomy are discussed.

Cardioprotective effects of exercise training on myofilament calcium activation in ovariectomized rats

2004 ◽  
Vol 96 (5) ◽  
pp. 1755-1760 ◽  
Author(s):  
Tepmanas Bupha-Intr ◽  
Jonggonnee Wattanapermpool
Keyword(s):  
Exercise Training ◽  
Adrenergic Receptors ◽  
Hormone Replacement ◽  
Left Ventricular ◽  
Ovariectomized Rats ◽  
Rat Hearts ◽  
Cardiac Myofilament ◽  
Cardioprotective Effects ◽  
Therapeutic Alternatives ◽  
Mgatpase Activity

The risks associated with hormone replacement therapy, especially cardiac diseases in postmenopausal women, have prompted extensive studies for other preventive or therapeutic alternatives. We investigated the cardioprotective effects of exercise training on the changes in cardiac myofilament Ca2+ activation in 10-wk-old ovariectomized rats. The exercise groups were subjected to a 9-wk running program on a motor-driven treadmill 1 wk after surgery. The relationship between pCa (-log molar free Ca2+ concentration) and myofibrillar MgATPase activity of exercise-sham myofibrils or exercise-ovariectomized myofibrils was the same and could not be distinguished from that of sedentary-sham control hearts. In contrast, a significant suppression in maximum MgATPase activity and a leftward shift of pCa50 (half-maximally activating pCa) in the pCa-ATPase activity relationship were detected in sedentary-ovariectomized rats. Exercise training also prevented the shift in myosin heavy chain (MHC) isoforms toward β-MHC in ovariectomized hearts. The upregulation of β1-adrenergic receptors in the left ventricular membranes of ovariectomized rat hearts, as measured by receptor binding and immunoblot analyses, was no longer observed in exercise-ovariectomized hearts. Immunoblot analyses of heat shock protein (HSP) 72, an inducible form of HSP70, demonstrated a significant downregulation in ovariectomized hearts. Exercise training in ovariectomized rats completely reversed the expression of HSP72 to the same level as sham controls. Our results clearly indicate the cardioprotective effects of exercise training on changes in cardiac myofilament Ca2+ activation in ovariectomized rats. Alterations in expression of β1-adrenergic receptors and HSP72 may, in part, play a mechanistic role in the cardioprotective effects.

Cardiac myofilament regulation by protein phosphatase type 1α and CapZ

2008 ◽  
Vol 86 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Fenghua Yang ◽  
David L. Aiello ◽  
W. Glen Pyle
Keyword(s):  
Protein Phosphatase ◽  
Troponin I ◽  
Troponin T ◽  
Immunoblot Analysis ◽  
Intracellular Signalling ◽  
General Role ◽  
Myosin Light Chain 2 ◽  
Cardiac Myofilament ◽  
Myofilament Activation ◽  
Protein Phosphatase Type

Myofilament regulation by protein kinases is well characterized, but relatively little is known about protein phosphatase control of myofilaments. Increased protein phosphatase type 1 (PP1) activity observed in failing hearts underscores the need for investigation of this intracellular signal, including the elements that regulate its activity. The Z-disc protein CapZ controls protein kinase C (PKC) regulation of cardiac myofilaments, but whether this effect is specific to PKC, or CapZ plays a general role in intracellular signalling, is not known. We sought to determine how the α isoform of PP1 (PP1α) regulates murine cardiac myofilaments and whether CapZ influences PP1α-dependent regulation of cardiac myofilaments. Immunoblot analysis showed PP1α binding to cardiac myofilaments. Exogenous PP1α increased myofilament Ca2+ sensitivity and maximal actomyosin Mg2+-ATPase activity while dephosphorylating myosin binding protein C, troponin T, troponin I, and myosin light chain 2. Extraction of CapZ decreased myofilament-associated PP1α and attenuated the effects of PP1α on myofilament activation. PP1α-dependent dephosphorylation of myofilament proteins was reduced with CapZ extraction, except for troponin I. Extracting CapZ after PP1α treatment allowed most of the PP1α-dependent effects on myofilament activation to remain, indicating that CapZ removal modestly desensitizes cardiac myofilaments to dephosphorylation. Our results demonstrate myofilament regulation by PP1α and support the concept that cardiac Z-discs are vital components in intracellular signalling.

scholarly journals Bisphenol S rapidly depresses heart function through estrogen receptor-β and decreases phospholamban phosphorylation in a sex-dependent manner

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Melissa Ferguson ◽  
Ilka Lorenzen-Schmidt ◽  
W. Glen Pyle
Keyword(s):  
Troponin I ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Partial Replacement ◽  
Dependent Manner ◽  
Bisphenol S ◽  
Ventricular Systolic Pressure ◽  
Cardiac Myofilament ◽  
Phospholamban Phosphorylation

Abstract The health effects of the endocrine disruptor Bisphenol A (BPA) led to its partial replacement with Bisphenol S (BPS) in several products including food containers, toys, and thermal paper receipts. The acute effects of BPS on myocardial contractility are unknown. We perfused mouse hearts from both sexes for 15 min with physiologically relevant doses of BPS or BPA. In females BPS (1 nM) decreased left ventricular systolic pressure by 5 min, whereas BPA (1 nM) effects were delayed to 10 min. BPS effects in male mice were attenuated. In both sexes ER-β antagonism abolished the effects of BPS. Cardiac myofilament function was not impacted by BPS or BPA in either sex, although there were sex-dependent differences in troponin I phosphorylation. BPS increased phospholamban phosphorylation at S16 only in female hearts, whereas BPA reduced phosphorylation in both sexes. BPA decreased phospholamban phosphorylation at T17 in both sexes while BPS caused dephosphorylation only in females. This is the first study to compare sex differences in the acute myocardial response to physiologically relevant levels of BPS and BPA, and demonstrates a rapid ability of both to depress heart function. This study raises concerns about the safety of BPS as a replacement for BPA.

Relaxin alters cardiac myofilament function through a PKC-dependent pathway

2009 ◽  
Vol 297 (1) ◽  
pp. H29-H36 ◽  
Author(s):  
Erynn E. Shaw ◽  
Philip Wood ◽  
Justyna Kulpa ◽  
Feng Hua Yang ◽  
Alastair J. Summerlee ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Troponin I ◽  
Troponin T ◽  
Immunoblot Analysis ◽  
Inotropic Effects ◽  
Myosin Binding Protein ◽  
Myofilament Function ◽  
Cardiac Myofilament ◽  
Intracellular Ca ◽  
Myofilament Activation

The pregnancy hormone relaxin (RLX) is a powerful cardiostimulatory peptide. Despite its well-characterized effects on the heart, the intracellular mechanisms responsible for RLX's positive inotropic effects are unknown. Cardiac myofilaments are the central contractile elements of the heart, and changes in the phosphorylation status of myofilament proteins are known to mediate changes in function. The first objective of this study was to determine whether RLX stimulates myofilament activation and alters the phosphorylation of one or more myofilament proteins. RLX works through a variety of intracellular signaling cascades in different tissue types. Protein kinases A (PKA) and C (PKC) are two common molecules implicated in RLX signaling and are known to affect myofilament function. Thus the second objective of this study was to determine whether RLX mediates its myocardial effects through PKA or PKC activation. Murine myocardium was treated with recombinant H2-RLX, and cardiac myofilaments were isolated. RLX increased cardiac myofilament force development at physiological levels of intracellular Ca2+ without altering myofilament ATP consumption. Myosin binding protein C, troponin T, and troponin I phosphorylation levels were increased with RLX treatment. Immunoblot analysis revealed an increase in myofilament-associated PKC-δ, decreases in PKC-α and -βII, but no effect on PKC-ε. Inhibition of PKC with chelerythrine chloride or PKC-δ with rottlerin prevented the RLX-dependent changes in myofilament function and protein phosphorylation. PKA antagonism with H-89 had no effect on the myofilament effects of RLX. This study is the first to show that RLX-dependent changes in myofilament-associated PKC alters myofilament activation in a manner consistent with its cardiostimulatory effects.

Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication

2007 ◽  
Vol 292 (2) ◽  
pp. R844-R851 ◽  
Author(s):  
Ariyaporn Thawornkaiwong ◽  
Jantarima Pantharanontaga ◽  
Jonggonnee Wattanapermpool
Keyword(s):  
Atpase Activity ◽  
Ovariectomized Rats ◽  
Myofibrillar Atpase ◽  
Diabetes Complication ◽  
Myofibrillar Atpase Activity ◽  
Rat Hearts ◽  
Cardiac Myofilament ◽  
Myofilament Activation ◽  
Cardioprotective Effects ◽  
Kinetics Of

The amelioration of cardioprotective effect of estrogen in diabetes suggests potential interactive action of estrogen and insulin on myofilament activation. We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar preparations from hearts of sham and 10-wk ovariectomized rats with or without simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats with estrogen and/or insulin supplementation. Similar magnitude of suppressed maximum myofibrillar ATPase activity was demonstrated in ovariectomized, diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and the relative suppression in α-myosin heavy chain level in ovariectomy combined with diabetes could be completely restored by estrogen and insulin supplementation. Conversely, the myofilament Ca2+ hypersensitivity detected only in the ovariectomized but not diabetic group was also observed in diabetic-ovariectomized rats, which was restored upon estrogen supplementation. Binding kinetics of β1-adrenergic receptors and immunoblots of β1-adrenoceptors as well as heat shock 72 (HSP72) were analyzed to determine the association of changes in receptors and HSP72 to that of the myofilament response to Ca2+. The amount of β1-adrenoceptors significantly increased concomitant with Ca2+ hypersensitivity of the myofilament, without differences in the receptor binding affinity among the groups. In contrast, changes in HSP72 paralleled that of maximum myofibrillar ATPase activity. These results indicate that hypersensitivity of cardiac myofilament to Ca2+ is specifically induced in ovariectomized rats even under diabetes complication and that alterations in the expression of β1-adrenoceptors may, in part, play a mechanistic role underlying the cardioprotective effects of estrogen that act together with Ca2+ hypersensitivity of the myofilament in determining the gender difference in cardiac activation.

Photocrosslinking of benzophenone-labeled single cysteine troponin I mutants to other thin filament proteins

2000 ◽  
Vol 296 (3) ◽  
pp. 899-910 ◽  
Author(s):  
Yin Luo ◽  
Jing-Lun Wu ◽  
Bing Li ◽  
Knut Langsetmo ◽  
John Gergely ◽  
...  
Keyword(s):  
Thin Filament ◽  
Troponin I ◽  
Thin Filament Proteins

scholarly journals Overexpression of troponin T in Drosophila muscles causes a decrease in the levels of thin-filament proteins

2005 ◽  
Vol 386 (1) ◽  
pp. 145-152 ◽  
Author(s):  
Raquel MARCO-FERRERES ◽  
Juan J. ARREDONDO ◽  
Benito FRAILE ◽  
Margarita CERVERA
Keyword(s):  
Thin Filament ◽  
Troponin I ◽  
Troponin T ◽  
Thin Filaments ◽  
Muscle Formation ◽  
Thin Filament Proteins ◽  
Flight Muscles ◽  
Transgenic Drosophila ◽  
Regulated Thin Filament

Formation of the contractile apparatus in muscle cells requires co-ordinated activation of several genes and the proper assembly of their products. To investigate the role of TnT (troponin T) in the mechanisms that control and co-ordinate thin-filament formation, we generated transgenic Drosophila lines that overexpress TnT in their indirect flight muscles. All flies that overexpress TnT were unable to fly, and the loss of thin filaments themselves was coupled with ultrastructural perturbations of the sarcomere. In contrast, thick filaments remained largely unaffected. Biochemical analysis of these lines revealed that the increase in TnT levels could be detected only during the early stages of adult muscle formation and was followed by a profound decrease in the amount of this protein as well as that of other thin-filament proteins such as tropomyosin, troponin I and actin. The decrease in thin-filament proteins is not only due to degradation but also due to a decrease in their synthesis, since accumulation of their mRNA transcripts was also severely diminished. This decrease in expression levels of the distinct thin-filament components led us to postulate that any change in the amount of TnT transcripts might trigger the down-regulation of other co-regulated thin-filament components. Taken together, these results suggest the existence of a mechanism that tightly co-ordinates the expression of thin-filament genes and controls the correct stoichiometry of these proteins. We propose that the high levels of unassembled protein might act as a sensor in this process.

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