Caspase-2 is a negative regulator of necroptosis.

The role of caspase-2 in cell death regulation remains largely unknown. In this study we have analyzed the involvement of caspase-2 in RIPK1-regulated necrosis (necroptosis) in human ovarian carcinoma cells. We show that these cells undergo necroptosis upon treatment with the DNA damaging drug cisplatin in combination with the pan-caspase inhibitor zVAD-fmk.

Involvement of mitophagy in cisplatin-induced cell death regulation.

Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. The removal of malfunctioning or damaged mitochondria is essential for normal cellular physiology and tissue development. Stimulation of mitochondrial permeabilization and release of proapoptotic factors from the intermembrane space is an essential step in triggering the mitochondrial pathway of cell death.

Effects of Laser Radiation on Mitochondria and Mitochondrial Proteins Subjected to Nitric Oxide.

The biological roles of heme and nonheme nitrosyl complexes in physiological and pathophysiological conditions as metabolic key players are considered in this study. Two main physiological functions of protein nitrosyl complexes are discussed-(1) a depot and potential source of free nitric oxide (NO) and (2) a controller of crucial metabolic processes. The first function is realized through the photolysis of nitrosyl complexes (of hemoglobin, cytochrome , or mitochondrial iron-sulfur proteins).

Jasmonate-responsive MYB factors spatially repress rutin biosynthesis in Fagopyrum tataricum.

Jasmonates are plant hormones that induce the accumulation of many secondary metabolites, such as rutin in buckwheat, via regulation of jasmonate-responsive transcription factors. Here, we report on the identification of a clade of jasmonate-responsive subgroup 4 MYB transcription factors, FtMYB13, FtMYB14, FtMYB15, and FtMYB16, which directly repress rutin biosynthesis in Fagopyrum tataricum. Immunoblot analysis showed that FtMYB13, FtMYB14, and FtMYB15 could be degraded via the 26S proteasome in the COI1-dependent jasmonate signaling pathway, and that this degradation is due to the SID motif in their C-terminus.

Cell death-based treatment of lung adenocarcinoma.

The most common type of lung cancer is adenocarcinoma (ADC), comprising around 40% of all lung cancer cases. In spite of achievements in understanding the pathogenesis of this disease and the development of new approaches in its treatment, unfortunately, lung ADC is still one of the most aggressive and rapidly fatal tumor types with overall survival less than 5 years. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors.

Cell death-based treatment of neuroblastoma.

Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and causes 15% of childhood cancer-related mortality. The main drivers of NB formation are neural crest cell-derived sympathoadrenal cells that undergo abnormal genetic arrangements. Moreover, NB is a complex disease that has high heterogeneity and is therefore difficult to target for successful therapy.

Impairment of Fas-ligand-caveolin-1 interaction inhibits Fas-ligand translocation to rafts and Fas-ligand-induced cell death.

Fas-ligand/CD178 belongs to the TNF family proteins and can induce apoptosis through death receptor Fas/CD95. The important requirement for Fas-ligand-dependent cell death induction is its localization to rafts, cholesterol- and sphingolipid-enriched micro-domains of membrane, involved in regulation of different signaling complexes. Here, we demonstrate that Fas-ligand physically associates with caveolin-1, the main protein component of rafts.

Two native types of phytochrome A, phyA' and phyA", differ by the state of phosphorylation at the N-terminus as revealed by fluorescence investigations of the Ser/Ala mutant of rice phyA expressed in transgenic Arabidopsis.

Phytochrome A (phyA) mediates different photoresponses what may be connected with the existence of its two types, phyA' and phyA'', differing by spectroscopic, photochemical and functional properties. We investigated a role of phyA phosphorylation in their formation turning to transgenic Arabidopsis thaliana (L. Heynh.

Modulation of Mcl-1 transcription by serum deprivation sensitizes cancer cells to cisplatin.

Background: The development of approaches that increase therapeutic effects of anti-cancer drugs is one of the most important tasks of oncology. Caloric restriction in vivo or serum deprivation (SD) in vitro has been shown to be an effective tool for sensitizing cancer cells to chemotherapeutic drugs. However, the detailed mechanisms underlying the enhancement of apoptosis in cancer cells by SD remain to be elucidated.

Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications.

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses.

Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta.

Vasoconstriction triggered by hydrogen sulfide: Evidence for Na,K,2Clcotransport and L-type Ca channel-mediated pathway.

Objectives: This study examined the dose-dependent actions of hydrogen sulfide donor sodium hydrosulphide (NaHS) on isometric contractions and ion transport in rat aorta smooth muscle cells (SMC).

Methods: Isometric contraction was measured in ring aortas segments from male Wistar rats. Activity of Na/K-pump and Na,K,2Clcotransport was measured in cultured endothelial and smooth muscle cells from the rat aorta as ouabain-sensitive and ouabain-resistant, bumetanide-sensitive components of the Rb influx, respectively.

Involvement of autophagy in the outcome of mitotic catastrophe.

Evading cell death is a major driving force for tumor progression that is one of the main problems in current cancer research. Mitotic catastrophe (MC) represents attractive platform compromising tumor resistance to current therapeutic modalities. MC appeared as onco-suppressive mechanism and is defined as a stage driving the cell to an irreversible destiny, i.

Mitophagy: Link to cancer development and therapy.

Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. Mitophagy is responsible for the removal of malfunctioning or damaged mitochondria, which is essential for normal cellular physiology and tissue development. Pathways involved in the regulation of mitophagy, tumorigenesis, and cell death are overlapping in many cases and may be triggered by common upstream signals, which converge at the mitochondria.

Post-translational Modification of Caspases: The Other Side of Apoptosis Regulation.

Apoptosis is a crucial program of cell death that controls development and homeostasis of multicellular organisms. The main initiators and executors of this process are the Cysteine-dependent ASPartate proteASES - caspases. A number of regulatory circuits tightly control caspase processing and activity.

Contrasting effects of glutamine deprivation on apoptosis induced by conventionally used anticancer drugs.

Tumor cells dependence on glutamine offers a rationale for their elimination via targeting of glutamine metabolism. The aim of this work was to investigate how glutamine deprivation affects the cellular response to conventionally used anticancer drugs. To answer this question, neuroblastoma cells were pre-incubated in a glutamine-free medium and treated with cisplatin or etoposide.

Caloric restriction - A promising anti-cancer approach: From molecular mechanisms to clinical trials.

Cancer is the second leading cause of death worldwide and the morbidity is growing in developed countries. According to WHO, >14 million people per year are diagnosed with cancer and about 8 million die. Anti-cancer strategy includes chemo-, immune- and radiotherapy or their combination.

Reactive oxygen species regulate a balance between mitotic catastrophe and apoptosis.

Mitotic catastrophe (MC) is a sequence of events resulting from premature or inappropriate entry of cells into mitosis that can be caused by chemical or physical stresses. There are several observations permitting to define MC as an oncosuppressive mechanism. MC can end up in apoptosis, necrosis or senescence.

Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation.

Macroautophagy/autophagy is a well-organized process of intracellular degradation, which is rapidly activated under starvation conditions. Recent data demonstrate a transcriptional upregulation of several autophagy genes as a mechanism that controls autophagy in response to starvation. Here we report that despite the significant upregulation of mRNA of the essential autophagy initiation gene ULK1, its protein level is rapidly reduced under starvation.

Tudor staphylococcal nuclease: biochemistry and functions.

Tudor staphylococcal nuclease (TSN, also known as Tudor-SN, SND1 or p100) is an evolutionarily conserved protein with invariant domain composition, represented by tandem repeat of staphylococcal nuclease domains and a tudor domain. Conservation along significant evolutionary distance, from protozoa to plants and animals, suggests important physiological functions for TSN. It is known that TSN is critically involved in virtually all pathways of gene expression, ranging from transcription to RNA silencing.

In one harness: the interplay of cellular responses and subsequent cell fate after quantum dot uptake.

Rapid growth and expansion of engineered nanomaterials will occur when the technology can be used safely. Quantum dots have excellent prospects in clinical applications, but the issue of toxicity has not yet been resolved. To enable their medical implementation, the effect on, and mechanisms in, live cells should be clearly known and predicted.

Targeting succinate:ubiquinone reductase potentiates the efficacy of anticancer therapy.

Mitochondria play a pivotal role in apoptosis: permeabilization of the outer mitochondrial membrane and the release of pro-apoptotic proteins from the intermembrane space of mitochondria are regarded as the key event in apoptosis induction. Here we demonstrate how non-toxic doses of the mitochondrial Complex II inhibitor thenoyltrifluoroacetone (TTFA), which specifically inhibits the ubiquinone-binding site of succinate dehydrogenase (SDH), synergistically stimulated cell death, induced by harmless doses of cisplatin in a panel of chemoresistant neuroblastoma cell lines. Apoptotic cell death was confirmed by cytochrome c release from the mitochondria, cleavage of poly ADP-ribose polymerase, processing of caspase-3, which is an important executive enzyme in apoptosis, and caspase-3-like activity.

New conjugates of polyene macrolide amphotericin B with benzoxaboroles: synthesis and properties.

A novel series of conjugates of the antifungal antibiotic amphotericin B (AmB) with benzoxaboroles was synthesized. Antifungal activity of new compounds was tested on yeastβ Candida albicans and Cryptococcus humicolus and filamentous fungi Aspergillus niger and Fusarium oxysporum using the broth microdilution method. The potency of di-modified derivatives against the tested strains was similar to that of the parent AmB.

Mitotic catastrophe and cancer drug resistance: A link that must to be broken.

An increased tendency of genomic alterations during the life cycle of cells leads to genomic instability, which is a major driving force for tumorigenesis. A considerable fraction of tumor cells are tetraploid or aneuploid, which renders them intrinsically susceptible to mitotic aberrations, and hence, are particularly sensitive to the induction of mitotic catastrophe. Resistance to cell death is also closely linked to genomic instability, as it enables malignant cells to expand even in a stressful environment.

Relaxation Photoprocesses in a Crowned Styryl Dye and its Metal Complex.

The effects of solvent and crown-ether moiety on spectral properties of pyridinium styryl dye were studied by steady-state absorption and fluorescent spectroscopy. Analysis of viscosity and polarity effects on fluorescence quantum yield and Stokes shift permitted us to suggest that there is a two stage process of excited state relaxation. The macrocyclic moiety has a little influence on the first stage of relaxation, which manifests itself in a magnitude of Stokes shift, but suppresses considerably the second stage, which manifests itself in a magnitude of fluorescence quantum yield.