1,721,043 research outputs found
The cardiovascular phenotype in fabry disease: New findings in the research field
No full textFabry disease (FD) is a lysosomal storage disorder, depending on defects in alphagalactosidase A (GAL) activity. At the clinical level, FD shows a high phenotype variability. Among them, cardiovascular dysfunction is often recurrent or, in some cases, is the sole symptom (cardiac variant) representing the leading cause of death in Fabry patients. The existing therapies, besides specific symptomatic treatments, are mainly based on the restoration of GAL activity. Indeed, mutations of the galactosidase alpha gene (GLA) cause a reduction or lack of GAL activity leading to globotriaosylceramide (Gb3) accumulation in several organs. However, several other mechanisms are involved in FD’s development and progression that could become useful targets for therapeutics. This review discusses FD’s cardiovascular phenotype and the last findings on molecular mechanisms that accelerate cardiac cell damage
Inflammation and cardiovascular diseases: The most recent findings
No full textThe series of reactive biological events that we identify as inflammation has been investigated in recent years and unveiled as an important mechanism for regeneration. The study of the underlying complexity has been boosted by new technological innovation in research and allowed the identification of inflammatory responses as the basis of diseases that were considered degenerative rather than regenerative in nature. This is the case for cardiovascular diseases, from the organ damage that follows an acute event to the damage of target organs exposed to chronic risk factors. This editorial explores innovative aspects of inflammation in the setup of cardiovascular risk factors and diseases
COMPOSIZIONE CELLULARE E STRUTTURA DEL PANCREAS ENDOCRINO DI ALCUNE SPECIE DI PESCI, ANFIBI E RETTILI DEL PARCO DEL MATESE
No full textThe role of the transcription factor nuclear factor kappa B in the regulation of cardiac hypertrophy
No full textCardiac hypertrophy is a maladaptive response to an injury, characterized by an increase in cell size, expression of fetal genes, fibrosis and apoptosis. Several signalling transduction pathways have been identified so far that are involved in this response and all of them converge on transcription factors that are the main regulator of the expression of hypertrophic genes. Among these, nuclear factor kappa B (NF-κB) is a key transcription factor regulating the expression of several genes involved in human inflammation and disease. Several reports have demonstrated the involvement of NF-κB in the regulation of cardiac hypertrophy, and different inhibitors of NF-κB activity have been described so far that are able to block NF-κB at different levels of its signalling transduction pathway. NF-κB inhibition is an effective strategy to reduce multiple aspects of cardiac hypertrophy such as cardiomyocyte size, fibrosis, inflammatory cytokines expression and apoptosis. This article focuses on recently described mechanisms of inhibition of NF-κB activity and their application to animal models of cardiac hypertrophy. All these reports add to the knowledge of NF-κB signalling and could be helpful for future studies that will be focused on the research of specific and non-toxic inhibitors of NF-κB activity to regulate cardiac hypertrophy and its evolution towards heart failure. © 2010 Adis Data Information BV. All rights reserved
Novel insights in β-adrenergic receptor signaling
No full textThe adrenergic receptors (ARs) are G-protein-coupled receptors that in response to stimuli activate several intracellular signaling regulating key biologic functions and affecting several pathological conditions, mainly cardiovascular diseases (CV). Indeed, almost 40% of approved drugs for the treatment of CV are based on adrenergic receptors targeting. Their discovery dates back to the beginning of the XX century but only in the last decades ARs signaling, function and regulation have been clarified. Generally, ARs signal through the cellular membrane to cytoplasmic G proteins. Besides this canonic pathway, it has been shown that activated ARs bind β-arrestins initiating desensitization, endocytosis and β-arrestin-dependent signaling. Thus, ARs are able to activate intracellular signaling in two different manners (through G-protein or β-arrestin), a phenomenon called “biased signaling.” In the last decades great advances have been made that increased the knowledge of ARs functions and their role in pathological conditions. The translation of these findings to clinic will be helpful to increase the specificity of the treatments of cardiac and vascular pathologies
A FUSION PROTEIN HAVING ANTITUMOR ACTIVITY
No full textThe invention relates to a fusion protein, designated as TAT-RH, comprising a first segment consisting of the minimal sequence of the HIV-TAT transduction domain and a second segment consisting of the RH region of the GRK5 kinase. Advantageously, the TAT- RH fusion protein is capable of penetrating into an eukaryotic cell without the help provided by vectors, and is capable of increasing cell apoptosis. These properties make the TAT-RH fusion protein according to the invention particularly suitable as an anti-tumor medicament. The invention further describes the nucleic acid sequence encoding for the TAT-RH fusion protein, a host cell transformed with the nucleic acid encoding for TAT- RH, as well as a method for the manufacture of TAT-RH by recombinant means
Calcium/calmodulin-dependent kinases can regulate the TSH expression in the rat pituitary
Full text linkPURPOSE: The endocrine secretion of TSH is a finely orchestrated process
controlled by the thyrotropin-releasing hormone (TRH). Its homeostasis and
signaling rely on many calcium-binding proteins belonging to the "EF-hand"
protein family. The Ca2+/calmodulin (CaM) complex is associated with
Ca2+/CaM-dependent kinases (Ca2+/CaMK). We have investigated Ca2+/CaMK
expression and regulation in the rat pituitary.
METHODS: The expression of CaMKII and CaMKIV in rat anterior pituitary cells was
shown by immunohistochemistry. Cultured anterior pituitary cells were stimulated
by TRH in the presence and absence of KN93, the pharmacological inhibitor of
CaMKII and CaMKIV. Western blotting was then used to measure the expression of
these kinases and of the cAMP response element-binding protein (CREB). TSH
production was measured by RIA after time-dependent stimulation with TRH. Cells
were infected with a lentiviral construct coding for CaMKIV followed by
measurement of CREB phosphorylation and TSH.
RESULTS: Our study shows that two CaM kinases, CaMKII and CaMKII, are expressed
in rat pituitary cells and their phosphorylation in response to TRH occurs at
different time points, with CaMKIV being activated earlier than CaMKII. TRH
induces CREB phosphorylation through the activity of both CaMKII and CaMKIV. The
activation of CREB increases TSH gene expression. CaMKIV induces CREB
phosphorylation while its dominant negative and KN93 exert the opposite effects.
CONCLUSION: Our data indicate that the expression of Ca2+/CaMK in rat anterior
pituitary are correlated to the role of CREB in the genetic regulation of TSH,
and that TRH stimulation activates CaMKIV, which in turn phosphorylates CREB.
This phosphorylation is linked to the production of thyrotropin
To NFκB or not to NFκB: The Dilemma on How to Inhibit a Cancer Cell Fate Regulator
No full textNuclear factor κB (NFκB) is a transcription factor that plays an important role in carcinogenesis as well as in the regulation of inflammatory response. NFκB is constitutively expressed in tumours where it induces the expression of genes which promote cell proliferation, apoptotic events, angiogenesis, invasion and metastasis. Furthermore, many cancer cells show aberrant or constitutive NFκB activation that mediates resistance to chemo- and radio-therapy. Therefore, the inhibition of NFκB activity appears a potential therapeutic strategy for cancer treatment. In this review, we focus on the role of NFκB in carcinogenesis and summarize actual inhibitors of NFκB that could be potential therapeutic target in cancer therapy
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