Search results for "Apoptosis."

Toward a Rational Design of Polyamine-Based Zinc-Chelating Agents for Cancer Therapies.

2020

In vitro viability assays against a representative panel of human cancer cell lines revealed that polyamines L1a and L5a displayed remarkable activity with IC50 values in the micromolar range. Preliminary research indicated that both compounds promoted G1 cell cycle arrest followed by cellular senescence and apoptosis. The induction of apoptotic cell death involved loss of mitochondrial outer membrane permeability and activation of caspases 3/7. Interestingly, L1a and L5a failed to activate cellular DNA damage response. The high intracellular zinc-chelating capacity of both compounds, deduced from the metal-specific Zinquin assay and ZnL2+ stability constant values in solution, strongly sup…

Identification of Biphenyl-Based Hybrid Molecules Able To Decrease the Intracellular Level of Bcl-2 Protein in Bcl-2 Overexpressing Leukemia Cells

2009

With the aim of enhancing the structural complexity and diversity of an existing collection of bi- and terphenyl compounds, we synthesized hybrid molecules comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on apoptosis and differentiation, making them potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

2015

Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, …

Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart.

2003

INTRODUCTION: Melatonin (MEL), a pineal hormone, is well known as a potent antioxidant in a variety of ischemia-reperfusion models. Recent studies have assumed a pivotal role of reactive oxygen species (ROS) in the development of apoptosis. There are few pieces of information concerning a possible protective role of MEL against apoptosis in ischemia-reperfusion injury of myocardium. METHODS: We conducted an in vitro experiment: (1) to study the effect of MEL in the model of isolated and perfused working rat heart; (2) to evaluate the antioxidant capacity of MEL by a simple fluorescence test; and (3) to analyze the extent of apoptosis inhibition by MEL. Four groups of male Wistar rat were us…

Focus on the unique mechanisms involved in thoracic aortic aneurysm formation in bicuspid aortic valve versus tricuspid aortic valve patients: clinic…

2013

OBJECTIVES: The involvement of different factors in the onset of thoracic aortic aneurysm (TAA) in patients with a bicuspid aortic valve (BAV) vs those with a tricuspid aortic valve (TAV) is well recognized. However, the molecular, genetic and cellular mechanisms driving TAA remain unclear. The aim of this study was to identify the different mechanisms involved in TAA development in patients with BAV vs TAV. METHODS: Aorta specimens and DNA samples were collected from 24 BAV (18 men and 6 women; mean age: 54.2 ± 14.39 years) and 110 TAV (79 men and 31 women, mean age: 66 ± 9.8 years) patients. A control group of 128 subjects (61 men and 67 woman, mean age: 61.1 ± 5.8 years) was also enrolle…

DNA replication arrest in response to genotoxic stress provokes early activation of stress-activated protein kinases (SAPK/JNK).

2009

Abstract The impact of DNA damage-induced replication blockage for early activation of stress kinases [stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK)] is largely unknown. Here, we show that induction of dual phosphorylation of SAPK/JNK by the DNA polymerase inhibitor aphidicolin was not ameliorated by additional exposure to ultraviolet (UV) light, indicating that overlapping mechanisms participate in signaling to SAPK/JNK triggered by both agents. UV-induced DNA replication blockage, cyclobutane pyrimidine dimer formation and DNA strand break induction coincided with SAPK/JNK phosphorylation at early (≤ 30 min) but not late (≥ 2 h) time points after exposure. Genotoxin…

Deficiency of glutathione peroxidase-1 accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice.

2007

Background— We have recently demonstrated that activity of red blood cell glutathione peroxidase-1 is inversely associated with the risk of cardiovascular events in patients with coronary artery disease. The present study analyzed the effect of glutathione peroxidase-1 deficiency on atherogenesis in the apolipoprotein E-deficient mouse. Methods and Results— Female apolipoprotein E-deficient mice with and without glutathione peroxidase-1 deficiency were placed on a Western-type diet for another 6, 12, or 24 weeks. After 24 weeks on Western-type diet, double-knockout mice (GPx-1 −/− ApoE −/− ) developed significantly more atherosclerosis than control apolipoprotein E-deficient mice. Moreover…

Apoptosis linfocitaria según receptor TCR- αβ y TCR- γδ en sujetos sanos

2015

Durante décadas, los LTγδ han generado cierto desconcierto debido a su preponderancia en los tejidos periféricos sobre la sangre periférica y a la presencia de fenotipos activados y de memoria mayoritariamente, así como por su capacidad para reconocer un amplio repertorio de antígenos, alguno de los cuales no requieren ser procesados por el MHC. Los LTγδ forman parte de un sistema inmunológico superpuesto entre la inmunidad innata y la adquirida. Estas células están en constante contacto con sustancias medioambientales, identificando posibles patógenos para presentarlos a otras células o eliminarlos (células T γδ activadas), memorizando su estructura antigénica para posteriores contactos (c…

Apoptosis rate in cumulus cells can be considerate as an indicator for the selection of embryos to improve ongoing pregnancy and implantation rate

2014

AN INNOVATIVE STRATEGY IN SELECTING OOCYTES WITH HIGH IMPLANTATION POTENTIALITY FOR INTRACYTOPLASMIC SPERM INJECTION PROCEDURE

2015

The aim of the research was to investigate the apoptosis rate of individual cumulus cell-oocyte complexes (COC), associated to the level of pAKT, to verify the difference between oocytes who produce embryos able to reach the blastocyst stage compared with embryos arrested during the in vitro culture. It was demonstrated that DNA fragmentation in cumulus cells was remarkably lower in patients who achieved a pregnancy after ICSI cycles, related to the quality of oocytes and embryos1,2. AKT pathway plays a critical role in the regulation of cell survival, and most growth factors activate this pathway3. The study focused on 53 patients, involved after informed consent. In this prospective and r…