Resveratrol prevents palmitic-acid-induced cardiomyocyte contractile impairment

2019 ◽  
Vol 97 (12) ◽  
pp. 1132-1140
Author(s):  
Xavier Lieben Louis ◽  
Pema Raj ◽  
Zach Meikle ◽  
Liping Yu ◽  
Shannel E. Susser ◽  
...  
Keyword(s):  
Protein Expression ◽  
Palmitic Acid ◽  
Troponin I ◽  
Contractile Function ◽  
Morphological Changes ◽  
Saturated Fatty Acids ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Pre Treatment ◽  
Hoechst Staining

Long-chain saturated fatty acids, especially palmitic acid (PA), contribute to cardiomyocyte lipotoxicity. This study tests the effects of PA on adult rat cardiomyocyte contractile function and proteins associated with calcium regulating cardiomyocyte contraction and relaxation. Adult rat cardiomyocytes were pretreated with resveratrol (Resv) and then treated with PA. For the reversal study, cardiomyocytes were incubated with PA prior to treatment with Resv. Cardiomyocyte contractility, ratio of rod- to round-shaped cardiomyocytes, and Hoechst staining were used to measure functional and morphological changes in cardiomyocytes. Protein expression of sarco-endoplasmic reticulum ATPase 2a (SERCA2a), native phospholamban (PLB) and phosphorylated PLB (pPLB ser16 and pPLB thr17), and troponin I (TnI) and phosphorylated TnI (pTnI) were measured. SERCA2a activity was also measured. Our results show that PA (200 μM) decreased the rate of cardiomyocyte relaxation, reduced the number of rod-shaped cardiomyocytes, and increased the number of cells with condensed nuclei; pre-treating cardiomyocytes with Resv significantly prevented these changes. Post-treatment with Resv did not reverse morphological changes induced by PA. Protein expression levels of SERCA2a, PLB, pPLBs, TnI, and pTnI were unchanged by PA or Resv. SERCA2a activity assay showed that Vmax and Iono ratio were increased with PA and pre-treatment with Resv prevented this increase. In conclusion, our results show that Resv protect cardiomyocytes from contractile dysfunction induced by PA.

Luteolin improves contractile function and attenuates apoptosis following ischemia–reperfusion in adult rat cardiomyocytes

2011 ◽  
Vol 668 (1-2) ◽  
pp. 201-207 ◽  
Author(s):  
Lingling Qi ◽  
Huanjun Pan ◽  
Dongye Li ◽  
Fang Fang ◽  
Dan Chen ◽  
...  
Keyword(s):  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Rat Cardiomyocytes ◽  
Adult Rat

In vivo adenoviral transfer of sorcin reverses cardiac contractile abnormalities of diabetic cardiomyopathy

2004 ◽  
Vol 286 (1) ◽  
pp. H68-H75 ◽  
Author(s):  
Jorge Suarez ◽  
Darrell D. Belke ◽  
Bernd Gloss ◽  
Thomas Dieterle ◽  
Patrick M. McDonough ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Myocyte ◽  
Viral Vector ◽  
Contractile Function ◽  
Cardiac Contractility ◽  
Rat Cardiomyocytes ◽  
Adenoviral Gene Transfer ◽  
Adult Rat ◽  
Adenoviral Transfer

In many types of heart failure cardiac myocyte Ca2+ handling is abnormal because of downregulation of key Ca2+-handling proteins like sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a and ryanodine receptor (RyR)2. The alteration in SERCA2a and RyR2 expression results in altered cytosolic Ca2+ transients, leading to abnormal contraction. Sorcin is an EF-hand protein that confers the property of caffeine-activated intracellular Ca2+ release in nonmuscle cells by interacting with RyR2. To determine whether sorcin could improve the contractile function of the heart, we overexpressed sorcin in the heart of either normal or diabetic mice and in adult rat cardiomyocytes with an adenoviral gene transfer approach. Sorcin overexpression was associated with an increase in cardiac contractility of the normal heart and dramatically rescued the abnormal contractile function of the diabetic heart. These effects could be attributed to an improvement of the Ca2+ transients found in the cardiomyocyte after sorcin overexpression. Viral vector-mediated delivery of sorcin to cardiac myocytes is beneficial, resulting in improved contractile function in diabetic cardiomyopathy.

scholarly journals Contractile Function is Altered by Regulation of HO-1 Activity in Single Adult Rat Cardiomyocytes

2010 ◽  
Vol 98 (3) ◽  
pp. 720a
Author(s):  
Sarah Nowakowski ◽  
F. Steven Korte ◽  
Jun Luo ◽  
Margaret Allen ◽  
Michael Regnier
Keyword(s):  
Contractile Function ◽  
Rat Cardiomyocytes ◽  
Adult Rat

scholarly journals Palmitic acid increases HCK protein and gene expression levels in vascular smoot muscle cells

2020 ◽  
Author(s):  
Ghasem Ghasempour ◽  
Fahimeh Zamani-Garmsiri ◽  
Asghar Mohammadi ◽  
Mohammad Najafi
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Palmitic Acid ◽  
Saturated Fatty Acids ◽  
Muscle Cells ◽  
Expression Levels ◽  
Vsmc Proliferation ◽  
Gene And Protein Expression ◽  
Oil Red O Staining ◽  
Gene Expression Levels

Abstract Background and Aims: Some saturated fatty acids are known to involve in atherosclerosis through different biologic pathways. The aim of this study was to investigate the effects of palmitic acid on the HCK gene and protein expression levels in vascular smooth muscle cells (VSMCs). Methods and Results: The cells were treated with palmitic acid (0.5 mM, 24 hours) on the cell viability assays. The HCK gene and protein expression levels were measured by real time q-PCR and western blot techniques, respectively. Oil Red O staining method was used to determine the intracellular lipid values. The HCK gene expression level was increased significantly in the PA-treated VSMCs (P 0.02). The total and phosphorylated HCK (p-HCK) protein expression levels increased in VSMCs. However, there was a significant increase in p-HCK value (P 0.001). Conclusion: The results showed that the palmitic acid increases p-HCK function so that it may affect the VSMC proliferation.

scholarly journals MiR-96-5p Induced by Palmitic Acid Suppresses the Myogenic Differentiation of C2C12 Myoblasts by Targeting FHL1

2020 ◽  
Vol 21 (24) ◽  
pp. 9445
Author(s):  
Mai Thi Nguyen ◽  
Kyung-Ho Min ◽  
Wan Lee
Keyword(s):  
Cell Cycle ◽  
Palmitic Acid ◽  
Transcriptional Activation ◽  
Morphological Changes ◽  
Myogenic Differentiation ◽  
Saturated Fatty Acids ◽  
Critical Role ◽  
C2c12 Myoblasts ◽  
Multi Stage ◽  
Myogenic Factors

Skeletal myogenesis is a multi-stage process that includes the cell cycle exit, myogenic transcriptional activation, and morphological changes to form multinucleated myofibers. Recent studies have shown that saturated fatty acids (SFA) and miRNAs play crucial roles in myogenesis and muscle homeostasis. Nevertheless, the target molecules and myogenic regulatory mechanisms of miRNAs are largely unknown, particularly when myogenesis is dysregulated by SFA deposition. This study investigated the critical role played by miR-96-5p on the myogenic differentiation in C2C12 myoblasts. Long-chain SFA palmitic acid (PA) significantly reduced FHL1 expression and inhibited the myogenic differentiation of C2C12 myoblasts but induced miR-96-5p expression. The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Interestingly, miR-96-5p suppressed FHL1 expression by directly targeting the 3’UTR of FHL1 mRNA. The transfection of an miR-96-5p mimic upregulated the expressions of cell cycle-related genes, such as PCNA, CCNB1, and CCND1, and increased myoblast proliferation. Moreover, the miR-96-5p mimic inhibited the expressions of myogenic factors, such as myoblast determination protein (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (MEF2C), and myosin heavy chain (MyHC), and dramatically impeded differentiation and fusion of myoblasts. Overall, this study highlights the role of miR-96-5p in myogenesis via FHL1 suppression and suggests a novel regulatory mechanism for myogenesis mediated by miRNA in a background of obesity.

Regulation of myocardial function by histidine-rich, calcium-binding protein

2004 ◽  
Vol 287 (4) ◽  
pp. H1705-H1711 ◽  
Author(s):  
Guo-Chang Fan ◽  
Kimberly N. Gregory ◽  
Wen Zhao ◽  
Woo Jin Park ◽  
Evangelia G. Kranias
Keyword(s):  
Heart Failure ◽  
Ryanodine Receptor ◽  
Calcium Binding ◽  
Recombinant Adenovirus ◽  
Contractile Function ◽  
Binding Protein ◽  
Human Heart Failure ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Protein Levels

Impaired sarcoplasmic reticulum (SR) Ca release has been suggested to contribute to the depressed cardiac function in heart failure. The release of Ca from the SR may be regulated by the ryanodine receptor, triadin, junctin, calsequestrin, and a histidine-rich, Ca-binding protein (HRC). We observed that the levels of HRC were reduced in animal models and human heart failure. To gain insight into the physiological function of HRC, we infected adult rat cardiac myocytes with a recombinant adenovirus that contains the full-length mouse HRC cDNA. Overexpression (1.7-fold) of HRC in adult rat cardiomyocytes was associated with increased SR Ca load (28%) but decreased SR Ca-induced Ca release (37%), resulting in impaired Ca cycling and depressed fractional shortening (36%) as well as depressed rates of shortening (38%) and relengthening (33%). Furthermore, the depressed basal contractile and Ca kinetic parameters in the HRC-infected myocytes remained significantly depressed even after maximal isoproterenol stimulation. Interestingly, HRC overexpresssion was accompanied by increased protein levels of junctin (1.4-fold) and triadin (1.8-fold), whereas the protein levels of ryanodine receptor, calsequestrin, phospholamban, and sarco(endo)plasmic reticulum Ca-ATPase remained unaltered. Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function.

scholarly journals Palmitic acid increases HCK gene and protein expression levels in vascular smooth muscle cells

2021 ◽  
Author(s):  
Ghasem Ghasempour ◽  
Fahimeh Zamani-Garmsiri ◽  
Asghar Mohammadi ◽  
Mohammad Najafi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Protein Expression ◽  
Smooth Muscle Cells ◽  
Palmitic Acid ◽  
Vascular Smooth Muscle Cells ◽  
Saturated Fatty Acids ◽  
Muscle Cells ◽  
Expression Levels ◽  
Gene And Protein Expression

Abstract Background and Aims: Saturated fatty acids are known to involve in atherosclerosis through different biologic pathways. The aim of this study was to investigate the effects of palmitic acid (PA) on the tyrosine-protein kinase (HCK) gene and protein expression levels in vascular smooth muscle cells (VSMCs). Methods: The human Vascular Smooth Muscle Cells (VSMC) were treated with palmitic acid (0.5 mM, 24 hours) based on the cellular viability studies. The HCK gene and protein expression levels were measured by real-time qRT-PCR and western blotting techniques, respectively. Oil Red O staining method was used to determine the intracellular lipid values.Results: The HCK gene expression level was increased significantly in the PA-treated VSMCs (p=0.02). The total and phosphorylated HCK (p-HCK) protein expression levels increased in VSMCs. There was a significant increase in p-HCK value (P=0.001). Conclusion: The results showed that the palmitic acid increases intracellular p-HCK value so that it may affect the HCK-mediated pathways in VSMCs.

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.

scholarly journals Soluble CD14 inhibits contractile function and insulin action in primary adult rat cardiomyocytes

2017 ◽  
Vol 1863 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Sabrina Overhagen ◽  
Marcel Blumensatt ◽  
Pia Fahlbusch ◽  
Daniella Herzfeld de Wiza ◽  
Heidi Müller ◽  
...  
Keyword(s):  
Insulin Action ◽  
Contractile Function ◽  
Soluble Cd14 ◽  
Rat Cardiomyocytes ◽  
Adult Rat

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.

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