1,721,181 research outputs found
Opioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster .3. Autocrine stimulation of prodynorphin gene expression by dynorphin B
No full textProdynorphin mRNA and dynorphin B expression have been previously shown to be greatly increased in cardiac myocytes of BIO 14.6 cardiomyopathic hamsters. Here we report that exogenous dynorphin B in duced a dose-dependent increase in prodynorphin mRNA levels and stimulated prodynorphin gene transcription in normal hamster myocytes. Similar responses were elicited by the synthetic selective kappa opioid receptor agonist U-50,488H. These effects were counteracted by the kappa opioid receptor antagonist Mr-1452 and were not observed in the presence of chelerythrine or calphostin C, two specific protein kinase C (PKC) inhibitors, Treatment of cardiomyopathic cells with Mr-1452 significantly decreased both prodynorphin mRNA levels and prodynorphin gene transcription. In control myocytes, dynorphin B induced the translocation of PKC-alpha to the nucleus and increased nuclear PKC activity without affecting the expression of PKC-delta, -epsilon, or -zeta. Acute release of either U-50,488H or dyn B over single normal or cardiomyopathic cells transiently increased the cytosolic Ca2+ concentration. A sustained treatment with each opioid agonist increased the cytosolic Ca2+ level for a more prolonged period in cardiomyopathic than in control myocytes and led to a depletion of Ca2+ from the sarcoplasmic reticulum in both groups of cells, The possibility that prodynorphin gene expression may affect the function of the cardiomyopathic cell through an autocrine mechanism is discussed
Sarcoplasmic reticulum Ca2+ ATPase gene expression to the rescue of myocardial contractility in hypothyroid associated heart failure
No full textOpioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster .2. Role of intracellular calcium loading
No full textWe have previously shown that prodynorphin gene expression was markedly increased in adult myocytes of BIO 14.6 cardiomyopathic hamsters and that nuclear protein kinase C (PKC) may be involved in the induction of this opioid gene, Here we report that the cytosolic Ca2+ concentration was significantly increased in resting and in KCl-depolarized cardiomyopathic myocytes compared with normal cells, In normal and in cardiomyopathic cells, KCl significantly increased prodynorphin mRNA levels and prodynorphin gene transcription, These effects were abolished by the Ca2+ channel blocker verapamil. In control myocytes, the KCl-induced increase in prodynorphin mRNA expression was in part attenuated by chelerythrine or calphostin C, two selective PKC inhibitors, In these cells, KCL induced the translocation of PKC-alpha into the nucleus, increasing nuclear PKC activity, In resting cardiomyopathic myocytes, the increase in prodynorphin mRNA levels and gene transcription were significantly attenuated by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethylester being completely abolished when the chelating agent was administered in the presence of PKC inhibitors, KCI and the PKC activator 1,2-dioctanoyl-sn-glycerol additively stimulated prodynorphin gene expression both in normal and in cardiomyopathic cells, Therefore, we conclude that PKC activation and intracellular Ca2+ overload may represent the two major signaling mechanisms involved in the induction of the prodynorphin gene in cardiomyopathic cells
Evaluation of opioid peptide gene expression by solution hybridization RNase protection.
No full textThe solution hybridization RNase protection assay may be considered a suitable method for both qualitative and quantitative analysis of mRNAs. In the present study we described an application of solution hybridization RNase protection assay to the quantitative analysis of prodynorphin mRNA, which encodes for the synthesis of prodynorphin, a common precursor for a number of opioid peptides. In the myocardial cell, stimulation of the K opioid is involved in the modulation of cytosolic calcium and pH homeostasis. In the present study, we found that prodynorphin mRNA, which encodes for the synthesis of a common precursor of opioid peptides interacting with K sites, is synthesized both in atrial and in ventricular tissue of the rat heart. In adult cultured rat ventricular cardiomyocytes, the level of prodynorphin mRNA did not differ from that detected in the original ventricular tissue. This finding indicates that the myocardial cell is an important source for prodynorphin gene expression and has the potential for an intrinsic synthesis of dynorphin-related peptides
SARS-CoV-2 and endothelial cell interaction in COVID-19: molecular perspectives
No full textSARS-CoV-2 is the agent responsible for the coronavirus disease (COVID-19), which has been declared a pandemic by the World Health Organization. The clinical evolution of COVID-19 ranges from asymptomatic infection to death. Older people and patients with underlying medical conditions, particularly diabetes, cardiovascular and chronic respiratory diseases are more susceptible to develop severe forms of COVID-19. Significant endothelial damage has been reported in COVID-19 and growing evidence supports the key pathophysiological role of this alteration in the onset and the progression of the disease. In particular, the impaired vascular homeostasis secondary to the structural and functional damage of the endothelium and its main component, the endothelial cells, contributes to the systemic pro-inflammatory state and the multiorgan involvement observed in COVID-19 patients. This review summarizes the current evidence supporting the proposition that the endothelium is a key target of SARS-CoV-2, with a focus on the molecular mechanisms involved in the interaction between SARS-CoV-2 and endothelial cells
Development of a green fluorescent reporter for the bio-assay of anti-cancer drugs with anti-oxidant activity
No full text
ELF-pulsed magnetic fields modulate opioid peptide gene expression in myocardial cells
No full textObjectives: Magnetic fields have been shown to affect cell proliferation and growth factor expression in cultured cells, Although the activation of endorphin systems is a recurring motif among the biological events elicited by magnetic fields, compelling evidence indicating that magnetic fields may modulate opioid gene expression is still lacking. We therefore investigated whether extremely low frequency (ELF) pulsed magnetic fields (PMF) may affect opioid peptide gene expression and the signaling pathways controlling opioid peptide gene transcription in the adult ventricular myocyte, a cell type behaving both as a target and as a source for opioid peptides. Methods: Prodynorphin gene expression was investigated in adult rat myocytes exposed to PMF by the aid of RNase protection and nuclear run-off transcription assays. In PMF-exposed nuclei, nuclear protein kinase C (PKC) activity was followed by measuring the phosphorylation rate of the acrylodan-labeled MARCKS peptide. The effect of PMF on the subcellular distribution of different PKC isozymes was assessed by immunoblotting. A radioimmunoassay procedure coupled to reversed-phase high performance liquid chromatography was used to monitor the expression of dynorphin B. Results: Here, we show that PMF enhanced myocardial opioid gene expression and that a direct exposure of isolated myocyte nuclei to PMF markedly enhanced prodynorphin gene transcription, as in the intact cell. The PMF action was mediated by nuclear PKC activation but occurred independently from changes in PKC isozyme expression and enzyme translocation. PMF also led to a marked increase in the synthesis and secretion of dynorphin B. Conclusions: The present findings demonstrate that an opioid gene is activated by myocyte exposure to PMF and that the cell nucleus and nuclear embedded PKC are a crucial target for the PMF action. Due to the wide ranging importance of opioid peptides in myocardial cell homeostasis, the current data may suggest consideration for potential biological effects of PMF in the cardiovascular system. (C) 2000 Elsevier Science B.V. All rights reserved
Non-coding RNAs as biomarkers of myocardial infarction
Full text linkNon-coding RNAs (ncRNAs) encompass a family of ubiquitous RNA molecules that lack protein-coding potential and have tissue-specific expression. A significant body of evidence indicates that ncRNA's aberrant expression plays a critical role in disease onset and development. NcRNAs' biochemical characteristics such as disease-associated concentration changes, structural stability, and high abundance in body fluids make them promising prognostic and diagnostic biomarkers. Myocardial infarction (MI) is a leading cause of mortality worldwide. Acute myocardial infarction (AMI), the term in use to describe MI's early phase, is generally diagnosed by physical examination, electrocardiogram (ECG), and the presence of specific biomarkers. In this regard, compared to standard MI biomarkers, such as the cardiac troponin isoforms (cTnT & cTnI) and the Creatinine Kinase (CK), ncRNAs appears to provide better sensitivity and specificity, ensuring a rapid and correct diagnosis, an earlier treatment, and consequently a good prognosis for the patients. This review aims to summarize and discuss the most promising and recent data on the potential clinical use of circulating ncRNAs as MI biomarkers. Specifically, we focused primarily on miRNAs and lncRNAs, highlighting their significant specificity and sensitivity, discussing their limitations, and suggesting possible overcoming approaches
Nuclear opioid receptors activate opioid peptide gene transcription in isolated myocardial nuclei
No full textOpioid-binding sites were identified in highly purified nuclei isolated from hamster ventricular myocardial cells. A significant increase in the maximal binding capacity for a kappa opioid receptor ligand was observed in myocardial nuclei from BIO 14.6 cardiomyopathic hamsters, as compared with nuclei obtained from normal myocytes of the F1B strain. The exposure of isolated nuclei to dynorphin B, a natural agonist of kappa opioid receptors, markedly increased opioid peptide gene transcription. The transcriptional effect was mediated by nuclear protein kinase C activation and occurred at a higher rate in nuclei from cardiomyopathic myocytes than in nuclei isolated from normal cells. Thus, a nuclear endorphinergic system may play an intracrine role in the regulation of gene transcription under both normal and pathological conditions
- …
