Search results for "APOPTOSI"

Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

2021

Abstract Aims  Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results  We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identif…

miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction

2014

Summary miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vasculari…

Cardiomyocyte apoptosis is related to left ventricular dysfunction and remodelling in dilated cardiomyopathy, but is not affected by growth hormone t…

2007

Background and aims Cardiomyocyte apoptosis (CA) is a common feature of end-stage heart failure. We examined whether CA is associated with cardiac dysfunction and remodelling in heart failure due to dilated cardiomyopathy and studied the effect of human growth hormone (hGH) on CA. Methods and results We studied 38 patients, included in a phase III multi-center, randomised, double-blind and placebo-controlled trial of biosynthetic hGH treatment in dilated cardiomyopathy, at baseline and after 14 weeks treatment. Twenty-six patients received hGH and 12 received placebo. CA was quantified in endomyocardial biopsies using the TUNEL assay. CA correlated with left ventricular size (r=0.43, p=0.00…

Differential responses to docosahexaenoic acid in primary and immortalized cardiac cells

2013

Abstract The importance of dietary polyunsaturated fatty acids (PUFAs) in the reduction of cardiovascular disease has been recognized for many years. Docosahexaenoic acid (22:6n3, DHA) is an n-3 PUFA known to affect numerous biological functions and provide cardioprotection; however, the exact molecular and cellular protective mechanism(s) remain unknown. In contrast, DHA also possesses many anti-tumorgenic properties including suppressing cell growth and inducing apoptosis. In the present study, we investigated the effect of DHA toward H9c2 cells (an immortalized cardiac cell line) and neonatal primary cardiomyocytes (NCM). Cells were treated with 0 μM, 10 μM or 100 μM DHA for upto 48 h. C…

Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondroc…

2019

Abstract Ethnopharmacological relevance Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. Materials and methods In vivo OA model was established by…

Type V collagen and protein kinase C η down-regulation in 8701-BC breast cancer cells.

2011

We previously reported that ductal infiltrating carcinomas (d.i.c.) of the human breast display profound modifications of the stromal architecture, associated with anomalous collagen composition. Among the major alterations observed in the interstitial collagen, the relative increase of type V collagen content was detected. When type V collagen was used as an ‘‘in vitro’’ substrate for 8701-BC d.i.c. cells, it appeared able to restrain cell growth, inhibit cell motility and invasion ‘‘in vitro’’, and modify the expression levels of genes coding for apoptosis factors, caspases and stress response proteins. In the present paper we demonstrate that type V collagen induces the down-regulation o…

Abstract 4219: Lysosomal membrane permeabilization, a novel anticancer mechanism induced by pterostilbene

2011

Abstract Pterostilbene (Pter) (3,5-dimethoxy-4′-hydroxystilbene), a natural dimethylated analog of resveratrol, is a phytoalexin abundant in plants and fruits with a number of potential benefits for human health. Darakchasava, an Indian herbal preparation of Vitis Vinifera, contains Pter and is prescribed as a cardiotonic in ayurvedic and traditional medicine. Furthermore, some observations indicate that Pter can be beneficial in the prevention and treatment of different diseases such as diabetes, dyslipidemia, or cancer. Pter shows higher bioavailability than resveratrol. The substitution of two OH groups (positions 3 and 5) by methyl groups increases the stabilityof the molecule and its r…

Quaderni del Dottorato di Ricerca in Oncobiologia Sperimentale: Tecniche e Procedure di Ricerca

2008

Survivin’s Dual Role: An Export’s View

2007

Survivin is proposed to function as a mitotic regulator and an apoptosis inhibitor during development and pathogenesis. As such, survivin has aroused keen interest in disparate areas of basic and translational research. Survivin acts as a subunit of the chromosomal passenger complex (CPC), composed of the mitotic kinase Aurora-B, Borealin and INCENP, and is essential for proper chromosome segregation and cytokinesis. Our recent findings indicate that the nuclear export receptor Crm1 is critically involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionary conserved in all mammalian survivin proteins. In addition, the survivin/…

A novel moniliformin derivative as pan-inhibitor of histone deacetylases triggering apoptosis of leukemia cells

2021

New and potent agents that evade multidrug resistance (MDR) and inhibit epigenetic modifications are of great interest in cancer drug development. Here, we describe that a moniliformin derivative (IUPAC name: 3-(naphthalen-2-ylsulfanyl)-4-{[(2Z)-1,3,3-trimethyl-2,3-dihydro-1H-indol-2-ylidene]methyl}cyclobut-3-ene-1,2-dione; code: MCC1381) bypasses P-gp-mediated MDR. Using transcriptomics, we identified a large number of genes significantly regulated in response to MCC1381, which affected the cell cycle and disturbed cellular death and survival. The potential targets of MCC1381 might be histone deacetylases (HDACs) as predicted by SwissTargetPrediction. In silico studies confirmed that MCC13…