scholarly journals Transient Upregulation of Protein Kinase C in Pressure-Overloaded Neonatal Rat Myocardium

2010 ◽  
pp. 25-33 ◽  
Author(s):  
B Hamplová ◽  
F Novák ◽  
F Kolář
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Left Ventricular Myocardium ◽  
Aortic Constriction ◽  
Cardiac Growth ◽  
Kinase C

Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms α, δ and ε in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of 32P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (105 × g) and nuclear-cytoskeletalmyofilament-enriched (103 × g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the 3rd day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCδ, which increased significantly at d10 in the cytosolic fraction at the expense of the membraneenriched fraction. It is concluded that PKCα, PKCδ and PKCε undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

PKC-lambda is the atypical protein kinase C isoform expressed by immature ventricle

1997 ◽  
Vol 272 (4) ◽  
pp. H1636-H1642
Author(s):  
V. O. Rybin ◽  
P. M. Buttrick ◽  
S. F. Steinberg
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Northern Blot ◽  
Blot Analysis ◽  
Northern Blot Analysis ◽  
Ventricular Myocardium ◽  
Adult Rat ◽  
Atypical Pkc ◽  
Kinase C ◽  
Pkc Zeta

We recently identified a developmental decline in protein kinase C (PKC) isoform expression, at the level of the protein, in rat ventricular myocardium. To investigate mechanisms regulating PKC isoform expression in cardiac tissue, this study uses Northern blot analysis to compare the abundance of PKC isoform mRNAs in neonatal and adult rat ventricular myocardium. PKC-epsilon protein and mRNA were detected in both neonatal and adult rat ventricular myocardial preparations. In contrast, coordinate postnatal declines in the abundance of PKC-alpha and PKC-delta proteins and transcripts were identified. An antiserum raised against the COOH-terminal sequence of PKC-zeta detected abundant immunoreactivity in neonatal, but not adult, ventricular myocytes. However, PKC-zeta transcripts were not detectable in the heart either by Northern blot analysis or a reverse transcriptase-polymerase chain reaction approach, indicating that neither the myocytes nor the contaminating cellular elements in the heart express PKC-zeta. Rather, PKC-lambda, another atypical PKC isoform that is structurally highly homologous to PKC-zeta, was detected at the protein and mRNA level in neonatal, but not adult, ventricular myocardium. Taken together, these results establish that developmental declines in calcium-sensitive, novel, and atypical PKC isoforms are paralleled by changes in the levels of the mRNAs encoding these proteins, suggesting transcriptional regulation of PKC during normal cardiac development. The results of this study further identify PKC-lambda as the atypical PKC isoform expressed by the immature ventricle.

scholarly journals Genetic Reduction in Left Ventricular Protein Kinase C-α and Adverse Ventricular Remodeling in Human Subjects

2018 ◽  
Vol 11 (3) ◽  
Author(s):  
Ray Hu ◽  
Michael P. Morley ◽  
Jeffrey Brandimarto ◽  
Nathan R. Tucker ◽  
Victoria A. Parsons ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ventricular Remodeling ◽  
Human Subjects ◽  
Left Ventricular ◽  
Kinase C

Subnanomolar concentration of VIP induces the nuclear translocation of protein kinase C in neonatal rat cortical astrocytes

1994 ◽  
Vol 39 (4) ◽  
pp. 355-363 ◽  
Author(s):  
Z. Oláh ◽  
Cs. Lehel ◽  
W. B. Anderson ◽  
D. E. Brenneman ◽  
D. v. Agoston
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Nuclear Translocation ◽  
Neonatal Rat ◽  
Kinase C ◽  
Cortical Astrocytes

P121 Pressure overload-induced functional and metabolic impairments in type 2 diabetic hearts are ameliorated by inhibition of xanthine oxidase

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
Y Igaki ◽  
M Tanno ◽  
H Kouzu ◽  
Y Tatekoshi ◽  
T Yano ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Xanthine Oxidase ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Dependent Manner ◽  
Phenylephrine Infusion ◽  
Type 2 Diabetic

Abstract Funding Acknowledgements SANWA KAGAKU KENKYUSHO Co., Ltd. Background   We have recently demonstrated that AMP deaminase (AMPD) is upregulated in OLETF, obese type 2 diabetic (T2DM) rats, and that the upregulated AMPD contributes to depletion of myocardial ATP at the time of pressure overload, leading to diastolic dysfunction.  On the other hand, AMPD promotes the formation of IMP from AMP, and IMP is in turn further converted to hypoxanthine and xanthine, substrates of xanthine oxidase (XO), which produces uric acid with ROS as a byproduct.  Based on these findings, we tested the hypothesis that inhibition of XO ameliorates the pressure overload-induced diastolic dysfunction in T2DM rats.  Methods and results Metabolomic analyses of the left ventricular myocardium revealed that levels of myocardial hypoxanthine and xanthine were significantly higher by 30% and 28%, respectively, in OLETF than in LETO, non-diabetic control rats, under the condition of pressure overloading (200-230 mmHg) induced by phenylephrine infusion. Myocardial XO activity in OLETF was 57.9% higher than that in LETO, and the activity was significantly attenuated by oral administration of topiroxostat, an XO inhibitor, at 0.1-0.5 mg/kg/day for 14 days in a dose-dependent manner.  Pressure volume loop analyses showed that the pressure overloading induced by phenylephrine infusion resulted in significantly higher LVEDP in OLETF than in LETO (18.3 ± 1.5 vs. 12.2 ± 1.3 mmHg, p < 0.05, n = 7), though LVEDPs at baseline were comparable in OLETF and LETO (5.6 ± 0.4 vs. 4.7 ± 0.7 mmHg).  Treatment with topiroxostat significantly suppressed the pressure overload-induced elevation of LVEDP in OLETF (18.3 ± 1.5 vs. 11.3 ± 1.1 mmHg, p < 0.05) but not in LETO.  Tau, the time constant of LV pressure decay, was significantly prolonged to 14.7 ± 0.7 ms (p < 0.05) by pressure overloading in OLETF but not in LETO, though baseline Tau values were similar in LETO and OLETF (6.1 ± 0.2 vs. 8.0 ± 0.4 ms).  The prolongation of Tau by pressure overloading in OLETF was significantly attenuated by treatment with topiroxostat.  Ea/Ees, an index for ventricular-arterial coupling, was higher in OLETF than in LETO (2.3 ± 0.3 vs. 1.6 ± 0.3, p < 0.05) under the condition of pressure overloading, and it was also improved by topiroxostat in OLETF (1.2 ± 0.2, p < 0.05).  Myocardial ATP content was lower in OLETF than in LETO under the condition of pressure overloading (2966 ± 400 vs. 1818 ± 171 nmol/g wet tissue, p < 0.05), but treatment with topiroxostat significantly restored the ATP level (2629 ± 307 nmo/g wet tissue). Conclusion:  In T2DM hearts, not only XO activity but also XO substrates are upregulated and upregulated AMPD may be involved in the upregulation.  Inhibition of XO ameliorates pressure overload-induced diastolic dysfunction and improves ventricular-arterial coupling most likely through augmented ATP preservation.

scholarly journals Cardiac contractile dysfunction and protein kinase C–mediated myofilament phosphorylation in disease and aging

2019 ◽  
Vol 151 (9) ◽  
pp. 1070-1080
Author(s):  
Vani S. Ravichandran ◽  
Himanshu J. Patel ◽  
Francis D. Pagani ◽  
Margaret V. Westfall
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Animal Models ◽  
Troponin I ◽  
Contractile Function ◽  
Pressure Overload ◽  
Human Myocardium ◽  
Brown Norway ◽  
Circulatory Support ◽  
Kinase C

Increases in protein kinase C (PKC) are associated with diminished cardiac function, but the contribution of downstream myofilament phosphorylation is debated in human and animal models of heart failure. The current experiments evaluated PKC isoform expression, downstream cardiac troponin I (cTnI) S44 phosphorylation (p-S44), and contractile function in failing (F) human myocardium, and in rat models of cardiac dysfunction caused by pressure overload and aging. In F human myocardium, elevated PKCα expression and cTnI p-S44 developed before ventricular assist device implantation. Circulatory support partially reduced PKCα expression and cTnI p-S44 levels and improved cellular contractile function. Gene transfer of dominant negative PKCα (PKCαDN) into F human myocytes also improved contractile function and reduced cTnI p-S44. Heightened cTnI phosphorylation of the analogous residue accompanied reduced myocyte contractile function in a rat model of pressure overload and in aged Fischer 344 × Brown Norway F1 rats (≥26 mo). Together, these results indicate PKC-targeted cTnI p-S44 accompanies cardiac cellular dysfunction in human and animal models. Interfering with PKCα activity reduces downstream cTnI p-S44 levels and partially restores function, suggesting cTnI p-S44 may be a useful target to improve contractile function in the future.

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