Increase of PPARδ by dopamine mediated via DA-1 receptor-linked phospholipase C pathway in neonatal rat cardiomyocytes

Lo, Sherman; Lee, Kung-Shing; Chen, Li‐Jen; Chen, Chih‐Hsiung

doi:10.1016/j.autneu.2013.04.013

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…It has been documented that ginsenoside, one of the active principles in ginseng, can improve systolic/diastolic function and enhance cardiac dP / dt through the opening of mitochondrial adenosine triphosphate-sensitive potassium channels [41], reduction in oxidative stress via inhibition of glutathione [42], and augmentation of cellular calcium influx [43]. The increase of cellular calcium influx is consistent with to our previous reports regarding PPAR δ related cardiac tonic actions [10, 11, 44]. …”

Section: Discussionsupporting

confidence: 89%

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

Lin

Cherng

Chen

et al. 2014

BioMed Research International

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Ginseng has been shown to be effective on cardiac dysfunction. Recent evidence has highlighted the mediation of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Thus, we are interested to investigate the role of PPARδ in ginseng-induced modification of cardiac contractility. The isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats were applied to measure the actions of ginseng ex vivo and in vivo. In normal rats, ginseng enhanced cardiac contractility and hemodynamic dP/dt max significantly. Both actions were diminished by GSK0660 at a dose enough to block PPARδ. However, ginseng failed to modify heart rate at the same dose, although it did produce a mild increase in blood pressure. Data of intracellular calcium level and Western blotting analysis showed that both the PPARδ expression and troponin I phosphorylation were raised by ginseng in neonatal rat cardiomyocyte. Thus, we suggest that ginseng could enhance cardiac contractility through increased PPARδ expression in cardiac cells.

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Section: Discussionsupporting

confidence: 89%

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

Lin

Cherng

Chen

et al. 2014

BioMed Research International

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“…Some studies suggest that PPARβ is highly expressed in PCa cells and is associated with cell cycle regulation and proliferation [50]. PLC influences the expression of PPARβ through Ca 2+ /cytosolic phospholipase A2, thus affecting glucose metabolism [51, 52]. Following PLCε knockdown, we observed a decreased level of PPARβ alone.…”

Section: Discussionmentioning

confidence: 65%

PLCε regulates prostate cancer mitochondrial oxidative metabolism and migration via upregulation of Twist1

Fan

Wang³

et al. 2019

J Exp Clin Cancer Res

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Background Metabolic rewiring is a common feature of many cancer types, including prostate cancer (PCa). Alterations in master genes lead to mitochondrial metabolic rewiring and provide an appealing target to inhibit cancer progression and improve survival. Phospholipase C (PLC)ε is a regulator of tumor generation and progression. However, its role in mitochondrial metabolism remains unclear. Methods The GEO, The Cancer Genome Atlas, and the GTEx databases were used to determine Twist1 mRNA levels in tumors and their non-tumor counterparts. Fifty-five PCa and 48 benign prostatic hypertrophy tissue samples were tested for the presence of PLCε and Twist1 immunohistochemically. An association between PLCε and Twist1 was determined by Pearson’s correlation analysis. PLCε was knocked down with a lentiviral short hairpin RNA. Mitochondrial activity was assessed by measuring the oxygen consumption rate. Western blotting analyses were used to measure levels of PPARβ, Twist1, phosphorylated (p)-Twist1, p-MEK, p-ERK, p-P38, and p-c-Jun N-terminal kinase (JNK). Cells were treated with inhibitors of MEK, JNK, and P38 MAPK, and an agonist and inhibitor of peroxisome proliferator activated receptor (PPAR) β, to evaluate which signaling pathways were involved in PLCε-mediated Twist1 expression. The stability of Twist1 was determined after blocking protein synthesis with cycloheximide. Reporter assays utilized E-cadherin or N-cadherin luciferase reporters under depletion of PLCε or Twist1. Transwell assays assessed cell migration. Finally, a nude mouse tumor xenograft assay was conducted to verify the role of PLCε in tumor formation. Results Our findings revealed that the expression of PLCε was positively associated with Twist1 in clinical PCa samples. PLCε knockdown promoted mitochondrial oxidative metabolism in PCa cells. Mechanistically, PLCε increased phosphorylation of Twist1 and stabilized the Twist1 protein through MAPK signaling. The transcriptional activity of Twist1, and the Twist1-mediated epithelial-to-mesenchymal transition, cell migration, and transcription regulation, were suppressed by PLCε knockdown and by blocking PPARβ nuclear translocation. The tumor xenograft assay demonstrated that PLCε depletion diminished PCa cell tumorigenesis. Conclusions These findings reveal an undiscovered physiological role for PLCε in the suppression of mitochondrial oxidative metabolism that has significant implications for understanding PCa occurrence and migration. Electronic supplementary material The online version of this article (10.1186/s13046-019-1323-8) contains supplementary material, which is available to authorized users.

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“…Once believed to be the master regulator of glucose and lipid metabolism, PPAR-γ is associated with the maturation and development of adipocytes, the deposition of lipids, glucose metabolism, insulin sensitivity and other related events [187]. PPAR-γ has been shown to be mediated by bile salts and dopamine via phospholipase C in a calcium dependent manner, with elevations in dopamine resulting in increased PPAR-γ in cardiac myocytes [188]. PPAR-α is abundantly expressed in skeletal muscle, liver and brain [189,190], and is associated with dyslipidemia, a condition often seen in autistic patients [190][191][192][193].…”

Section: The Role Of Energy Metabolismmentioning

confidence: 99%

L1-79 and the Role of Catecholamines in Autism

Rothman¹

2021

Autism Spectrum Disorder - Profile, Heterogeneity, Neurobiology and Intervention

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A growing body of evidence supports a role for catecholaminergic dysfunction in the core symptoms of autism spectrum disorder (ASD). This paper reviews the direct and indirect role of catecholamines on the central and peripheral nervous systems in ASD. Catecholamines innervate every tissue in the body and almost all tracts of the brain, providing a common neurologic regulatory mechanism for all ASD symptoms. Because the morphology of the catecholaminergic synapse is regulated by growth factors that are released contemporaneously with neurotransmitters, an event that results in abnormally large catecholamine release, will also release high levels of growth factors, which can result in the budding and arborization of nerve terminals. Here, we hypothesize that a hypertrophic synaptic morphology can occur in catecholaminergic systems and increase catecholaminergic tone throughout the body, resulting in an imbalance between catecholaminergic neurologic mechanisms and those that oppose them, and consequently pathology. By exerting a presynaptic effect to inhibit tyrosine hydroxylase and thus the synthesis, storage and release of all catecholamines, L1–79 (a tyrosine hydroxylase inhibitor) may diminish neurotransmitter release and its associated growth factors exerting a therapeutic effect on ASD by reducing the hypertrophic morphology of the synapse and bringing catecholamines back into a homeostatic balance with oppositional neurologic and metabolic influences.

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Increase of PPARδ by dopamine mediated via DA-1 receptor-linked phospholipase C pathway in neonatal rat cardiomyocytes

Cited by 3 publications

References 38 publications

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

PLCε regulates prostate cancer mitochondrial oxidative metabolism and migration via upregulation of Twist1

L1-79 and the Role of Catecholamines in Autism

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