scholarly journals The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jingsheng Liang ◽  
Katarzyna Kazmierczak ◽  
Ana I. Rojas ◽  
Yingcai Wang ◽  
Danuta Szczesna-Cordary
Keyword(s):  
Papillary Muscle ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Contractile Force ◽  
Cardiac Troponin I ◽  
Wild Type ◽  
Partial Loss ◽  
Left And Right ◽  
The Difference ◽  
State Force

We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine) mutation in human cardiac troponin I (cTnI) on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV) and right (RV) ventricles of homozygous R21C+/+knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT) mice. There were no differences in the Ca2+sensitivity between the RV and LV of R21C+/+mice; however, the Ca2+sensitivity of force was higher in RV-R21C+/+compared with RV-WT and lower in LV- R21C+/+compared with LV-WT. We also observed partial loss of Ca2+regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC) was significantly higher in the RV versus LV of R21C+/+mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

scholarly journals A dominantly negative mutation in cardiac troponin I at the interface with troponin T causes early remodeling in ventricular cardiomyocytes

2014 ◽  
Vol 307 (4) ◽  
pp. C338-C348 ◽  
Author(s):  
Hongguang Wei ◽  
J.-P. Jin
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Wild Type ◽  
Leukemia Inhibitory Factor Receptor ◽  
Cell Width ◽  
Potent Effect ◽  
Western Blots ◽  
Adrenergic Response

We previously reported a point mutation substituting Cys for Arg111 in the highly conserved troponin T (TnT)-contacting helix of cardiac troponin I (cTnI) in wild turkey hearts (Biesiadecki et al. J Biol Chem 279: 13825–13832, 2004). This dominantly negative TnI-TnT interface mutation decreases the binding affinity of cTnI for TnT, impairs diastolic function, and blunts the β-adrenergic response of cardiac muscle (Wei et al. J Biol Chem 285: 27806–27816, 2010). Here we further investigate cellular phenotypes of transgenic mouse cardiomyocytes expressing the equivalent mutation cTnI-K118C. Functional studies were performed on single adult cardiomyocytes after recovery in short-term culture from isolation stress. The amplitude of contraction and the velocities of shortening and relengthening were lower in cTnI-K118C cardiomyocytes than wild-type controls. The intracellular Ca2+ transient was slower in cTnI-K118C cardiomyocytes than wild-type cells. cTnI-K118C cardiomyocytes also showed a weaker β-adrenergic response. The resting length of cTnI-K118C cardiomyocytes was significantly greater than that of age-matched wild-type cells, with no difference in cell width. The resting sarcomere was not longer, but slightly shorter, in cTnI-K118C cardiomyocytes than wild-type cells, indicating longitudinal addition of sarcomeres. More tri- and quadrinuclei cardiomyocytes were found in TnI-K118C than wild-type hearts, suggesting increased nuclear divisions. Whole-genome mRNA array and Western blots detected an increased expression of leukemia inhibitory factor receptor-β in the hearts of 2-mo-old cTnI-K118C mice, suggesting a signaling pathway responsible for the potent effect of cTnI-K118C mutation on early remodeling in cardiomyocytes.

scholarly journals R21C Mutation in Cardiac Troponin I Imposes Differences in the Degree of Order and Kinetics of Myosin Cross-Bridges of Left and Right Ventricles

2015 ◽  
Vol 108 (2) ◽  
pp. 293a
Author(s):  
Divya Duggal ◽  
Janhavi Nagwekar ◽  
Ryan Rich ◽  
Sangram Raut ◽  
Rafal Fudala ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Cardiac Troponin I ◽  
Left And Right ◽  
Cross Bridges ◽  
Kinetics Of ◽  
Degree Of Order

Developmental expression of rat cardiac troponin I mRNA

Development ◽  
1991 ◽  
Vol 112 (4) ◽  
pp. 1041-1051
Author(s):  
S. Ausoni ◽  
C. De Nardi ◽  
P. Moretti ◽  
L. Gorza ◽  
S. Schiaffino
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Mammalian Species ◽  
Calcium Sensitivity ◽  
Cardiac Troponin I ◽  
Developmental Expression ◽  
Adrenergic Stimulation ◽  
Adult Heart ◽  
Amino Terminal ◽  
The Difference

We have isolated and sequenced a full-length cDNA clone of rat cardiac troponin I (TnI). The amino acid sequence of rat cardiac TnI is highly similar to that of other mammalian species in the portion of the molecule (residues 33–210) that is also homologous to skeletal muscle TnI isoforms. In contrast, a lower degree of similarity is present in the cardiac TnI-specific amino terminal extension (residues 1–32). This region contains a conserved serine residue that has been shown to be selectively phosphorylated by cAMP-dependent protein kinase. Cardiac TnI mRNA is weakly expressed in the 18-day fetal heart and accumulates in neonatal and postnatal stages. No difference can be demonstrated between TnI mRNAs present in fetal and postnatal heart by RNAase protection assays. The fetal and neonatal, but not the adult heart, contain significant amounts of slow skeletal TnI transcripts, detected by oligonucleotide probes specific for the 5′- and 3′-untranslated regions of slow skeletal TnI mRNA. In situ hybridization studies show that cardiac and slow skeletal TnI mRNAs are coexpressed in the rat heart from embryonic day 11 throughout fetal and perinatal stages. Changes in troponin isoform expression during development may be responsible for the difference in calcium sensitivity and in the response to beta-adrenergic stimulation between fetal and adult heart.

Abstract 433: Regulatory and Elastic Protein Modifications in the Myocardium of Hibernating 13-lined Ground Squirrels

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Maighdlin R Patterson ◽  
Jonathan R Groening ◽  
Mark A Hiske ◽  
Hannah V Carey ◽  
Karen L Ball ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Ground Squirrels ◽  
Myocardial Stiffness ◽  
Sds Page ◽  
Filling Time ◽  
The Difference

The 13-lined ground squirrel exhibits remarkable cardiac adaptation during hibernation, periods of torpor being interrupted by repeated inter-bout arousal (IBA). During IBA heart rate rises from 2-4 bpm to as great as 300 bpm. This rise in heart rate occurs over just 5 hours and remains elevated for 12-24 hours before returning to the lower heart rate. With such rapid and marked changes in heart rate, and thus filling time, myocardial stiffness and relaxation must be regulated within a short timeframe. The objective of this work was to establish post-translational modifications (PTMs) in two proteins critical to myocardial stiffness and relaxation; titin and cardiac troponin I (TnI). It was specifically hypothesized that phosphorylation during IBA would be similar to that of summer tissue and distinct from tissue isolated during torpor. Left ventricular tissue (summer, n=9; torpor, n=10; IBA, n=7) was solubilized and separated by either 2-12% gradient SDS-Page (titin) or 12.5% SDS-PAGE (TnI). Total titin phosphorylation was measured via Pro-Q Diamond Phosphoprotein/SYPRO Ruby staining. PKA-specific TnI phosphorylation was quantified via western blotting, using a primary antibody specific to Ser 23,24. While there was a tendency toward decreased total titin phosphorylation in IBA, the difference was not significant. In contrast, there were significant group effects in PKA-specific TnI phosphorylation. Phospho-TnI/Total TnI ratios were lower in torpor when compared to summer (0.22±0.12 vs. 0.68±0.,34, p<0.05). While there was no significant difference between summer and IBA (0.62±0.35), the difference between torpor and IBA failed to reach significance. This data supports the hypothesis that rapid changes in heart rates are associated with changes in cardiac troponin-I phosphorylation, a modification that contributes to rapid rates of relaxation. Further dissection of site specific titin phosphorylation will be required to assess the extent to which PTM modify titin associated stiffness. Results from this work may have significant implications in our understanding of altered compliance in human heart failure.

scholarly journals Role of serum cardiac Troponin-I for risk stratification in first attack in acute myocardial infarction

1970 ◽  
Vol 8 (3) ◽  
pp. 57-63
Author(s):  
Md Sahabuddin Joarder ◽  
Md Jafarullah ◽  
Ahmed Moinuddin
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Outcome Evaluation ◽  
Cardiac Troponin I ◽  
The Mean ◽  
The Difference ◽  
Q Wave

Introduction: Cardiac troponin-I (cTnI) is known to have the highest specificity and analytic sensitivity for detection of myocardial injury; it is used both as diagnostic and prognostic marker. This study was aimed to confirm this idea. Subjects & methods: This prospective observational study included 60 patients of 40 to 65 years age range diagnosed as acute myocardial infarction. The mean ages were 50±8 years and 53±8 years in Q -wave AMI and non Q-wave AMI respectively. Male and female patients included were 86.7% and 13.3%; BMI was 25.3±1.5. Results: Study showed troponin-I 7.53±0.086 ng/ml in Q wave and in non Q-wave AMI was 6.38±0.64 ng/ml after 24 hours of attack of AMI without any significant difference between two groups (P>0.05). The mean troponin-I within 9 hours of attack, were 1.60±0.80 ng/ml and 2.7±1.4 ng/ml in stable and unstable group respectively and the difference found statistically significant (P<0.05). The mean troponin-I between 9-24 hours of attack were 2.90±1.20 ng/ml and 4.90±3.20 ng/ml in stable and unstable group respectively and the difference found statistically significant (P<0.01). The mean troponin-I in unstable group after 24 hours was 9.20±4.30 ng/ml which was more than between 9-24 hours and the difference was significant (P>0.001). In clinicopathological outcome evaluation 37 patients had troponin-I level >1.5 ng/ml in which 29 patients developed unstability and 8 patients were stable. Conclusion: Serum cTnI is better and more characteristic biomarker for risk prediction and prognosis evaluation in AMI patients. Key words: Cardiac Troponin-I, acute myocardial infarction, risk stratification.   DOI: 10.3329/bjms.v8i3.3984 Bangladesh Journal of Medical Sciences Vol.8(3) 2009 p57-63

scholarly journals A Comparative Study Between Conventional and Direct Stenting by Measuring Serum Cardiac Troponin-I

2012 ◽  
Vol 7 (1) ◽  
pp. 23-27
Author(s):  
Syeda Fahmida Afrin ◽  
Md Hasanur Rahman ◽  
Syed Dawoo Md Taimur ◽  
Muhsina Abdullah ◽  
Safia Sharmin ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Coronary Intervention ◽  
Cardiac Troponin I ◽  
Direct Stenting ◽  
Percutaneous Coronary ◽  
The Mean ◽  
The Difference ◽  
Serum Cardiac Troponin

The aim of the study is to assess serum Cardiac Troponin-I level in patients who have underdone Percutaneous coronary intervention (PCI) as an indication of myocardial injury and. Compare the troponin-I level in direct or conventional stetting in PCI and assess the superiorty of two methods of PCI, regarding myocardial injury and outcome. Cardiac Troponin-I (cTnI) is known to have the highest specificity & analytic sensitivity for detection of myocardial injury. This study was aimed to compare between conventional and direct stenting by assessing of serum cTnI. This observentional study was carried out in the Deparment of Biochemistry, Dhaka Medical College & Dept. of Cardiology, Ibrahim Cardiac Hospital and Research Institute during the period from July 2007 to June 2008. In this study we enrolled 60 diagnosed cases of coronary heart disease patients which were grouped as direct stenting (30 patients) and conventional stenting (30 patients) group. In this study, the age of the patients ranged from 42-72 years with a mean of 56.7 (±7.1) years. Male and female participants were 44 and 16 respectively. The mean left ventricular ejection fraction of them were 55.43 (±7.9) %. The difference of the mean troponin-I level before direct and conventional stenting was similar. Although the mean level of troponin-I after conventional stenting was higher (0.081± 0.042) than that of direct stenting (0.066±0.042), the difference of means was not statically significant (P> 0.05). Significant difference was observed between the mean before and after direct stenting as well as conventional stenting. From our observation we can conclude that serum cTnI level was higher after conventional stenting than that of direct stenting but the difference of means was not statically significant. It rises significantly after Percutaneous coronary intervention regardless of the type of procedure, whether direct or conventional stenting. Though the clinical outcome is reported to be similar in direct and conventional stenting, the direct stenting requires less procedural and equipment cost as well as less exposure time to radiation. DOI: http://dx.doi.org/10.3329/uhj.v7i1.10206 UHJ 2011; 7(1): 23-27

scholarly journals Cardiac troponin-I phosphorylation underlies myocardial contractile dysfunction induced by hypothermia rewarming

2019 ◽  
Vol 317 (4) ◽  
pp. H726-H731 ◽  
Author(s):  
Torkjel Tveita ◽  
Grace M. Arteaga ◽  
Young-Soo Han ◽  
Gary C. Sieck
Keyword(s):  
Diastolic Function ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Contractile Dysfunction ◽  
Stroke Work ◽  
Wild Type ◽  
Surface Cooling

Rewarming the intact heart after a period of hypothermia is associated with reduced myocardial contractility, decreased Ca2+ sensitivity, and increased cardiac troponin-I (cTnI) phosphorylation. We hypothesized that hypothermia/rewarming (H/R) induces left ventricular (LV) contractile dysfunction due to phosphorylation of cTnI at Ser23/24. To test this hypothesis, the response of wild-type mice ( n = 7) to H/R was compared with transgenic (TG) mice expressing slow skeletal TnI (TG-ssTnI; n = 7) that lacks the Ser23/24 phosphorylation sites. Hypothermia was induced by surface cooling and maintained at 23–25°C for 3 h. Subsequently, the animals were rewarmed to 37°C. LV systolic and diastolic function was assessed using a 1.4 F pressure-volume Millar catheter introduced via the right carotid artery. At baseline conditions, there were no significant differences in LV systolic function between wild-type and TG-ssTnI mice, whereas measurements of diastolic function [isovolumic relaxation constant (τ) and end-diastolic pressure-volume relationship (EDPVR)] were significantly ( P < 0.05) reduced in TG-ssTnI animals. Immediately after rewarming, significant differences between groups were found in cardiac output (CO; wild-type 6.6 ± 0.7 vs. TG-ssTnI 8.8 ± 0.7 mL/min), stroke work (SW; wild-type 796 ± 112 vs. TG-ssTnI 1208 ± 67 mmHg/μL), and the preload recruited stroke work (PRSW; wild-type 38.3 ± 4.9 vs. TG-ssTnI 68.8 ± 8.2 mmHg). However, EDPVR and τ returned to control levels within 1 h in both groups. We conclude that H/R-induced LV systolic dysfunction results from phosphorylation of cTnI at Ser23/24. NEW & NOTEWORTHY Rewarming following a period of accidental hypothermia leads to a form of acute cardiac failure (rewarming shock), which is in part due to reduced sensitivity to Ca2+ activation of myocardial contraction. The results of the present study support the hypothesis that rewarming shock is due to phosphorylation of cardiac troponin I.

scholarly journals NH2-terminal truncations of cardiac troponin I and cardiac troponin T produce distinct effects on contractility and calcium homeostasis in adult cardiomyocytes

2015 ◽  
Vol 308 (5) ◽  
pp. C397-C404 ◽  
Author(s):  
Hongguang Wei ◽  
J.-P. Jin
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Molecular Conformation ◽  
Troponin T ◽  
Cardiac Troponin I ◽  
Terminal Region ◽  
Cardiac Troponin T ◽  
Wild Type ◽  
Regulatory Structure ◽  
Ejection Time

Cardiac troponin I (TnI) has an NH2-terminal extension that is an adult heart-specific regulatory structure. Restrictive proteolytic truncation of the NH2-terminal extension of cardiac TnI occurs in normal hearts and is upregulated in cardiac adaptation to hemodynamic stress or β-adrenergic deficiency. NH2-terminal truncated cardiac TnI (cTnI-ND) alters the conformation of the core structure of cardiac TnI similarly to that produced by PKA phosphorylation of Ser23/24 in the NH2-terminal extension. At organ level, cTnI-ND enhances ventricular diastolic function. The NH2-terminal region of cardiac troponin T (TnT) is another regulatory structure that can be selectively cleaved via restrictive proteolysis. Structural variations in the NH2-terminal region of TnT also alter the molecular conformation and function. Transgenic mouse hearts expressing NH2-terminal truncated cardiac TnT (cTnT-ND) showed slower contractile velocity to prolong ventricular rapid-ejection time, resulting in higher stroke volume. Our present study compared the effects of cTnI-ND and cTnT-ND in cardiomyocytes isolated from transgenic mice on cellular morphology, contractility, and calcium kinetics. Resting cTnI-ND, but not cTnT-ND, cardiomyocytes had shorter length than wild-type cells with no change in sarcomere length. cTnI-ND, but not cTnT-ND, cardiomyocytes produced higher contractile amplitude and faster shortening and relengthening velocities in the absence of external load than wild-type controls. Although the baseline and peak levels of cytosolic Ca2+ were not changed, Ca2+ resequestration was faster in both cTnI-ND and cTnT-ND cardiomyocytes than in wild-type control. The distinct effects of cTnI-ND and cTnT-ND demonstrate their roles in selectively modulating diastolic or systolic functions of the heart.

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