10 Mitogen-activated protein kinases are activated by oxidative stress and cytokines in neonatal rat ventricular myocytes

1997 ◽  
Vol 25 (4) ◽  
pp. S566-S566 ◽  
Author(s):  
Angela CLERK ◽  
Peter H. SUGDEN
Keyword(s):  
Oxidative Stress ◽  
Protein Kinases ◽  
Ventricular Myocytes ◽  
Neonatal Rat ◽  
Mitogen Activated Protein Kinases ◽  
Rat Ventricular Myocytes ◽  
Mitogen Activated Protein ◽  
Neonatal Rat Ventricular Myocytes

scholarly journals Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes

1998 ◽  
Vol 333 (3) ◽  
pp. 581-589 ◽  
Author(s):  
Angela CLERK ◽  
Ashour MICHAEL ◽  
Peter H. SUGDEN
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Ventricular Myocytes ◽  
Small Heat Shock Protein ◽  
Neonatal Rat ◽  
Mitogen Activated Protein ◽  
Powerful Activator ◽  
Neonatal Rat Ventricular Myocytes ◽  
Stimulation Of

We investigated the activation of three subfamilies of mitogen-activated protein kinases (MAPKs), namely the stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs), the extracellularly responsive kinases (ERKs) and p38-MAPK, by oxidative stress as exemplified by H2O2 in primary cultures of neonatal rat ventricular myocytes. The 46 and 54 kDa species of SAPKs/JNKs were activated 5- and 10-fold, respectively, by 0.1 mM H2O2 (the maximally effective concentration). Maximal activation occurred at 15–30 min, but was still detectable after 2 h. Both ERK1 and ERK2 were activated 16-fold by 0.1 mM H2O2 with a similar time course to the SAPKs/JNKs, and this was comparable with their activation by 1 µM PMA, the most powerful activator of ERKs that we have so far identified in these cells. The activation of ERKs by H2O2 was inhibited by PD98059, which inhibits the activation of MAPK (or ERK) kinases, and by the protein kinase C (PKC) inhibitor, GF109203X. ERK activation was also inhibited by down-regulation of PMA-sensitive PKC isoforms. p38-MAPK was activated by 0.1 mM H2O2 as shown by an increase in its phosphorylation. However, maximal phosphorylation (activation) was more rapid (< 5 min) than for the SAPKs/JNKs or the ERKs. We studied the downstream consequences of p38-MAPK activation by examining activation of MAPK-activated protein kinase 2 (MAPKAPK2) and phosphorylation of the MAPKAPK2 substrate, the small heat shock protein HSP25/27. As with p38-MAPK, MAPKAPK2 was rapidly activated (maximal within 5 min) by 0.1 mM H2O2. This activation was abolished by 10 µM SB203580, a selective inhibitor of certain p38-MAPK isoforms. The phosphorylation of HSP25/27 rapidly followed activation of MAPKAPK2 and was also inhibited by SB203580. Phosphorylation of HSP25/27 was associated with a decrease in its aggregation state. These data indicate that oxidative stress is a powerful activator of all three MAPK subfamilies in neonatal rat ventricular myocytes. Activation of all three MAPKs has been associated with the development of the hypertrophic phenotype. However, stimulation of p38-MAPK and the consequent phosphorylation of HSP25/27 may also be important in cardioprotection.

CARP Plays a Key Role in Cellular Growth Under Hypertrophic Stimuli in Neonatal Rat Ventricular Myocytes

2013 ◽  
Vol 9 ◽  
Author(s):  
Tara A Shrout
Keyword(s):  
Gene Expression ◽  
Ventricular Myocytes ◽  
Cellular Growth ◽  
Neonatal Rat ◽  
Transcriptional Level ◽  
Dual Nature ◽  
Hypertrophic Growth ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes ◽  
Over Time

Cardiac hypertrophy is a growth process that occurs in response to stress stimuli or injury, and leads to the induction of several pathways to alter gene expression. Under hypertrophic stimuli, sarcomeric structure is disrupted, both as a consequence of gene expression and local changes in sarcomeric proteins. Cardiac-restricted ankyrin repeat protein (CARP) is one such protein that function both in cardiac sarcomeres and at the transcriptional level. We postulate that due to this dual nature, CARP plays a key role in maintaining the cardiac sarcomere. GATA4 is another protein detected in cardiomyocytes as important in hypertrophy, as it is activated by hypertrophic stimuli, and directly binds to DNA to alter gene expression. Results of GATA4 activation over time were inconclusive; however, the role of CARP in mediating hypertrophic growth in cardiomyocytes was clearly demonstrated. In this study, Neonatal Rat Ventricular Myocytes were used as a model to detect changes over time in CARP and GATA4 under hypertrophic stimulation by phenylephrine and high serum media. Results were detected by analysis of immunoblotting. The specific role that CARP plays in mediating cellular growth under hypertrophic stimuli was studied through immunofluorescence, which demonstrated that cardiomyocyte growth with hypertrophic stimulation was significantly blunted when NRVMs were co-treated with CARP siRNA. These data suggest that CARP plays an important role in the hypertrophic response in cardiomyocytes.

Abstract 15280: Comparisons of Action Potentials and Ionic Currents Between Neonatal Rat Ventricular Myocytes and Adult Zebrafish Ventricular Myocytes

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Adonis Z Wu ◽  
Shien-Fong Lin ◽  
Sheng-Nan Wu
Keyword(s):  
Electrical Properties ◽  
Ventricular Myocytes ◽  
Ionic Currents ◽  
Firing Frequency ◽  
Neonatal Rat ◽  
Adult Zebrafish ◽  
Patch Clamp Technique ◽  
Action Current ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes

Introduction: Zebrafish heart is established as a model to investigate cardiac electrical abnormalities. However, electrical properties of adult zebrafish cardiomyocytes are not sufficiently characterized. Hypothesis: In this study, by comparing the electrical properties between neonatal rat ventricular myocytes (NRVMs) and adult zebrafish ventricular myocytes (AZVMs), we intended to characterize the action potential (AP), action current (AC) and the properties of Na + current ( I Na ) in AZVMs. Methods: We used patch-clamp technique to characterize the electrical properties, including AP, AC and I Na , in cultured NRVMs and freshly isolated AZVMs. Results: NVRMs showed larger AP amplitude (119±6 vs. 79±4mV, p<.05) but shorter AP duration (APD 90 , 136±11 vs. 213±19 ms, p<.05) than those of AZVMs. The AP duration exhibited marked frequency-dependent alterations in AZVMs. Under the slow pacing rate, early after-depolarizations (EAD) emerged under slow pacing rate with 0.05 Hz. In cell-attached voltage-clamp recordings made from AZVMs, ACs could be elicited by +10 mV steps. As the depolarization step increased to +70 mV, the latency for appearance of ACs was progressively reduced from >123 ms to 9.8 ms. The presence of spontaneous ACs was monitored in spontaneously beating NRVMs and AZVMs. The AC amplitude in NRVMs was larger compared to that in AZVMs (17.3±2.1 vs. 11.6±1.1 pA, p<.05), although firing frequency of AC in NRVMs is higher than in AZVMs (1.13±0.09 vs. 0.38±0.03 Hz, p<.05). The lowering effect of ranolazine, a I Na antagonist, on firing frequency was significantly larger in NRVMs (1.13±0.09 to 0.31±0.02 Hz, p<.05) than in AZVMs (0.38±0.03 to 0.27±0.02 Hz). There was a hyperpolarizing shift of peak I Na in AZVM compared to NRVM. Conclusions: Our results demonstrated major differences in the cellular electrical behavior between AZVMs and NRVMs.

scholarly journals Chronotropic Response of Cultured Neonatal Rat Ventricular Myocytes to Short-Term Fluid Shear

2006 ◽  
Vol 46 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Ilka Lorenzen-Schmidt ◽  
Geert W. Schmid-Schönbein ◽  
Wayne R. Giles ◽  
Andrew D. McCulloch ◽  
Shu Chien ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Neonatal Rat ◽  
Fluid Shear ◽  
Short Term ◽  
Chronotropic Response ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes

scholarly journals Hexokinase–mitochondrial interactions regulate glucose metabolism differentially in adult and neonatal cardiac myocytes

2013 ◽  
Vol 142 (4) ◽  
pp. 425-436 ◽  
Author(s):  
Guillaume Calmettes ◽  
Scott A. John ◽  
James N. Weiss ◽  
Bernard Ribalet
Keyword(s):  
Cardiac Tissue ◽  
Ventricular Myocytes ◽  
Glycogen Synthesis ◽  
Neonatal Rat ◽  
Metabolic Profiles ◽  
Rat Ventricular Myocytes ◽  
Glycolytic Activity ◽  
Extracellular Glucose ◽  
Functional Consequences ◽  
Neonatal Rat Ventricular Myocytes

In mammalian tumor cell lines, localization of hexokinase (HK) isoforms to the cytoplasm or mitochondria has been shown to control their anabolic (glycogen synthesis) and catabolic (glycolysis) activities. In this study, we examined whether HK isoform differences could explain the markedly different metabolic profiles between normal adult and neonatal cardiac tissue. We used a set of novel genetically encoded optical imaging tools to track, in real-time in isolated adult (ARVM) and neonatal (NRVM) rat ventricular myocytes, the subcellular distributions of HKI and HKII, and the functional consequences on glucose utilization. We show that HKII, the predominant isoform in ARVM, dynamically translocates from mitochondria and cytoplasm in response to removal of extracellular glucose or addition of iodoacetate (IAA). In contrast, HKI, the predominant isoform in NRVM, is only bound to mitochondria and is not displaced by the above interventions. In ARVM, overexpression of HKI, but not HKII, increased glycolytic activity. In neonatal rat ventricular myocytes (NVRM), knockdown of HKI, but not HKII, decreased glycolytic activity. In conclusion, differential interactions of HKI and HKII with mitochondria underlie the different metabolic profiles of ARVM and NRVM, accounting for the markedly increased glycolytic activity of NRVM.

Sign in / Sign up

Export Citation Format

Share Document