Effect of Indapamide on Cyclic Adenosine 3',5'-Monophosphate Signal Transduction System in Isolated Adult Rat Cardiomyocytes from Normal Myocardium and Cardiac Hypertrophy

1993 ◽  
Vol 22 (12) ◽  
pp. 35-41 ◽  
Author(s):  
Simon W. Rabkin
Keyword(s):  
Signal Transduction ◽  
Cardiac Hypertrophy ◽  
Normal Myocardium ◽  
Signal Transduction System ◽  
Rat Cardiomyocytes ◽  
Adult Rat

PKC-independent signal transduction pathways increase SERCA2 expression in adult rat cardiomyocytes

2005 ◽  
Vol 39 (6) ◽  
pp. 911-919 ◽  
Author(s):  
Attia Anwar ◽  
Gerhild Taimor ◽  
Hüdayi Korkususz ◽  
Rolf Schreckenberg ◽  
Tobias Berndt ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Rat Cardiomyocytes ◽  
Adult Rat

Modification of Ca2+-handling in cardiomyocytes by redox sensitive mechanisms in response to ouabain

2013 ◽  
Vol 91 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Harjot K. Saini-Chohan ◽  
Larry Hryshko ◽  
Yan-Jun Xu ◽  
Naranjan S. Dhalla
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Redox Status ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Kinase C ◽  
Transduction Mechanisms

We examined the role of redox-sensitive signal transduction mechanisms in modifying the changes in [Ca2+]i produced by ouabain upon incubating adult rat cardiomyocytes with antioxidants or inhibitors of different protein kinases and monitoring alterations in fura-2 fluorescence. Ouabain increased basal [Ca2+]i, augmented the KCl-induced increase in [Ca2+]i, and promoted oxyradical production in cardiomyocytes. These actions of ouabain were attenuated by an oxyradical scavenging mixture (superoxide dismutase plus catalase), and the antioxidants (N-acetyl-l-cysteine and N-(2-mercaptoproprionyl)glycine). An inhibitor of MAP kinase (PD98059) depressed the ouabain-induced increase in [Ca2+], whereas inhibitors of tyrosine kinase (tyrphostin and genistein) and PI3 kinase (Wortmannin and LV294002) enhanced the ouabain-induced increase in [Ca2+]i. Inhibitors of protein kinase C (calphostin and bisindolylmalaimide) augmented the ouabain-induced increase in [Ca2+]i, whereas stimulation of protein kinase C by a phorbol ester (phorbol 12-myristate 13-acetate) depressed the action of ouabain. These results suggest that ouabain-induced inhibition of Na +–K+ ATPase may alter the redox status of cardiomyocytes through the production of oxyradicals, and increase the activities of various protein kinases. Thus, these redox-sensitive signal transduction mechanisms involving different protein kinases may modify Ca2+-handling sites in cardiomyocytes and determine the magnitude of net increase in [Ca2+]i in response to ouabain.

scholarly journals Effects of IGF-1 onIKandIK1Channels via PI3K/Akt Signaling in Neonatal Cardiac Myocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Richard M. Millis ◽  
Zikiar V. Alvin ◽  
Aiqiu Zhao ◽  
Georges E. Haddad
Keyword(s):  
Signal Transduction ◽  
Cardiac Hypertrophy ◽  
Cardiac Myocytes ◽  
Potassium Currents ◽  
Akt Signaling ◽  
Inward Rectifier ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Inward Rectifier Potassium Channels ◽  
Transduction Mechanisms

Previous studies suggest that sarcolemmal potassium currents play important roles in cardiac hypertrophy. IGF-1 contributes to cardiac hypertrophy via activation of PI3K/Akt signaling. However, the relationships between IGF-1, PI3K/Akt signaling and sarcolemmal potassium currents remain unknown. Therefore, we tested the hypothesis that IGF-1 and PI3K/Akt signaling, independently, decrease sarcolemmal potassium currents in cardiac myocytes of neonatal rats. We compared the delayed outward rectifier (IK) and the inward rectifier (IK) current densities resulting from IGF-1 treatments to those resulting from simulation of PI3K/Akt signaling using adenoviral (Ad) BD110 and wild-type Akt and to those resulting from inhibition of PI3K signaling by LY294002. Ad.BD110 and Ad.Akt decreasedIKand these decrements were attenuated by LY 294002. The IGF-1 treatments decreased bothIKandIK1but only theIKdecrement was attenuated by LY294002. These findings demonstrate that IGF-1 may contribute to cardiac hypertrophy by PI3K/Akt signal transduction mechanisms in neonatal rat cardiomyocytes. Failure of LY294002 to effectively antagonize IGF-1 induced decrements inIK1suggests that a signal pathway adjunct to PI3K/Akt contributes to IGF-1 protection against arrhythmogenesis in these myocytes. Our findings imply that sarcolemmal outward and inward rectifier potassium channels are substrates for IGF-1/PI3K/Akt signal transduction molecules.

scholarly journals Impact of PCSK9 on CTRP9-Induced Metabolic Effects in Adult Rat Cardiomyocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Susanne Rohrbach ◽  
Ling Li ◽  
Tatyana Novoyatleva ◽  
Bernd Niemann ◽  
Fabienne Knapp ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Protein Expression ◽  
Mitochondrial Biogenesis ◽  
Metabolic Effects ◽  
Lipid Lowering ◽  
Rat Cardiomyocytes ◽  
Adult Rat

The adipocytokine adiponectin and its structural homologs, the C1q/TNF-related proteins (CTRPs), increase insulin sensitivity, fatty acid oxidation and mitochondrial biogenesis. Adiponectin- and CTRP-induced signal transduction has been described to involve the adiponectin receptors and a number of co-receptors including the Low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is another target of the proprotein convertase subtilisin/kexin-9 (PCSK9) in addition to the LDL-receptor (LDL-R). Here, we investigated the influence of PCSK9 on the metabolic effects of CTRP9, the CTRP with the highest homology to adiponectin. Knockdown of LRP1 in H9C2 cardiomyoblasts blunts the effects of CTRP9 on signal transduction and mitochondrial biogenesis, suggesting its involvement in CTRP9-induced cellular effects. Treatment of adult rat cardiomyocytes with recombinant PCSK9 but not knockdown of endogenous PCSK9 by siRNA results in a strong reduction in LRP1 protein expression and subsequently reduces the mitochondrial biogenic effect of CTRP9. PCSK9 treatment (24 h) blunts the effects of CTRP9-induced signaling cascade activation (AMP-dependent protein kinase, protein kinase B). In addition, the stimulating effects of CTRP9 on cardiomyocyte mitochondrial biogenesis and glucose metabolism (GLUT-4 translocation, glucose uptake) are largely blunted. Basal fatty acid (FA) uptake is strongly reduced by exogenous PCSK9, although protein expression of the PCSK9 target CD36, the key regulator of FA transport in cardiomyocytes, is not altered. In addition, only minor effects of PCSK9 were observed on CTRP9-induced FA uptake or the expression of genes involved in FA metabolism or uptake. Finally, this CTRP9-induced increase in CD36 expression occurs independent from LRP1 and LDL-R. In conclusion, PCSK9 treatment influences LRP1-mediated signaling pathways in cardiomyocytes. Thus, therapeutic PCSK9 inhibition may provide an additional benefit through stimulation of glucose metabolism and mitochondrial biogenesis in addition to the known lipid-lowering effects. This could be an important beneficial side effect in situations with impaired mitochondrial function and reduced metabolic flexibility thereby influencing cardiac function.

Modification of gene expression in rat cardiomyocytes by linoleic and docosahexaenoic acids

2019 ◽  
Vol 97 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Sukhinder K. Cheema ◽  
Paramjit S. Tappia ◽  
Naranjan S. Dhalla
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Docosahexaenoic Acid ◽  
Cardiac Hypertrophy ◽  
Palmitic Acid ◽  
Nuclear Factor ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Expression Of Genes

Regulation of cardiac fatty acid metabolism is central to the development of cardiac hypertrophy and heart failure. We investigated the effects of select fatty acids on the expression of genes involved in immediate early as well as inflammatory and hypertrophic responses in adult rat cardiomyocytes. Cardiac remodeling begins with upregulation of immediate early genes for c-fos and c-jun, followed by upregulation of inflammatory genes for nuclear factor kappa B (NF-κB) and nuclear factor of activated T-cells (NFAT). At later stages, genes involved in hypertrophic responses, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are upregulated. Adult rat cardiomyocytes were treated with palmitic acid, a saturated fatty acid; oleic acid, a monounsaturated fatty acid; linoleic acid, a polyunsaturated fatty acid belonging to the n-6 class; and docosahexaenoic acid, a polyunsaturated fatty acid belonging to the n-3 class. Linoleic acid produced a greater increase in the mRNA expression of c-fos, c-jun, NF-κB, NFAT3, ANP, and BNP relative to palmitic acid and oleic acid. In contrast, docosahexaenoic acid caused a decrease in the expression of genes involved in cardiac hypertrophy. Our findings suggest that linoleic acid may be a potent inducer of genes involved in cardiac hypertrophy, whereas docosahexaenoic acid may be protective against the cardiomyocyte hypertrophic response.

Cooperative interaction between reactive oxygen species and Ca2+ signals contributes to angiotensin II-induced hypertrophy in adult rat cardiomyocytes

2012 ◽  
Vol 302 (4) ◽  
pp. H901-H909 ◽  
Author(s):  
Rukhsana Gul ◽  
Asif Iqbal Shawl ◽  
Suhn-Hee Kim ◽  
Uh-Hyun Kim
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Ang Ii ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Adp Ribosyl Cyclase

Reactive oxygen species (ROS) and Ca2+ signals are closely associated with the pathogenesis of cardiac hypertrophy. However, the cause and effect of the two signals in cardiac hypertrophy remain to be clarified. We extend our recent report by investigating a potential interaction between ROS and Ca2+ signals utilizing in vitro and in vivo angiotensin II (ANG II)-induced cardiac hypertrophy models. ANG II-induced initial Ca2+ transients mediated by inositol trisphosphate (IP3) triggered initial ROS production in adult rat cardiomyocytes. The ROS generated by activation of the NAD(P)H oxidase complex via Rac1 in concert with Ca2+ activates ADP-ribosyl cyclase to generate cyclic ADP-ribose (cADPR). This messenger-mediated Ca2+ signal further augments ROS production, since 2,2′-dihydroxyazobenzene, an ADP-ribosyl cyclase inhibitor, or 8-Br-cADPR, an antagonistic analog of cADPR, abolished further ROS production. Data from short hairpin RNA (shRNA)-mediated knockdown of Akt1 and p47phox demonstrated that Akt1 is the upstream key molecule responsible for the initiation of Ca2+ signal that activates p47phox to generate ROS in cardiomyocytes. Nuclear translocation of nuclear factor of activated T-cell in cardiomyocytes was significantly suppressed by treatment with NAD(P)H oxidase inhibitors as well as by shRNA against Akt1 and p47phox. Our results suggest that in cardiomyocytes Ca2+ and ROS messengers generated by ANG II amplify the initial signals in a cooperative manner, thereby leading to cardiac hypertrophy.

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