Aluminum ; toxicity ; Cell Death ; drug effects ; Humans ; Neurons ; drug effects

Isobavachalcone (IBC) or (E)-1-[2,4-dihydroxy-3-(3-methyl-2-butenyl)-phenyl]-3-(4-hydroxyphenyl)-2-propen-1-one or (E)-4,2',4'-trihydroxy-3'-prenylchalcone; 2',4,4'-trihydroxy-3'-prenyl-transchalcone, is a prenylated chalcone of the class flavonoid, firstly isolated from Psoralea corylifolia in 1968. IBC is known to possess a wide spectrum of biological activities, antibacterial, antifungal, anticancer, anti-reverse transcriptase, antitubercular and antioxidant. The compound was isolated from plant families, mostly Moraceae and Fabaceae. This review brings out together the knowledge on IBC, and can serve as the start point for future research and valorization accomplishments.
Animals ; Biosynthetic Pathways ; drug effects ; Cell Death ; drug effects ; Chalcones ; biosynthesis ; chemistry ; pharmacology ; Humans

OBJECTIVETo study whether necroptosis exists or not in neural cell death induced by aluminum.

METHODSSH-SY5Y cells were treated with 4 mmol/L AlCl(3) x 6H(2)O The cell viability was determined with CCK-8 kit after treated with Nec-1 at different dosages (0, 30, 60, 90 micromol/L). Mitochondria membrane potential (MMP), content of reactive oxygen species (ROS), and apoptotic rate/necrotic rates were measured with cytometry.

RESULTSNec-1 ameliorated the necrotic-like cell morphology, the cell viability were 0.28 +/- 0.05, 0.58 +/- 0.03, 0.68 +/- 0.04, and 1.03 +/- 0.17, there were significant differences between the Nec-1 treated groups and that of controls (t values were 3.25, 3.36, 4.56; P < 0.05). After Nec-1 treatment, the necrotic rates were 16.46% +/- 0.54%, 10.40% +/- 0.64%, 5.43% +/- 0.68%, and 6.28% +/- 0.35%, there were significant differences between the Nec-1 treated cells and that of controls (t values were 3.62, 7.32, 6.96; P < 0.05); while the apoptotic rates were 8.68 +/- 0.36, 7.66 +/- 0.53, 5.68 +/- 0.41, and 4.13 +/- 0.41, there was no significant difference among the groups (F = 6.33, P = 0.11). Cytometry had shown the increased cell MMPs after Nec-1 treatment, which were 67.54 +/- 6.36, 49.42 +/- 5.96, 84.79 +/- 6.86, and 95.51 +/- 7.01, there were significant differences as comparing MMPs of the middle and high dosage of Nec-1 treated cells with those of controls (t values were 3.21, 4.01; P < 0.05); while ROS contents in the Nec-1 treated SH-SY5Y cells were 54.07 +/- 3.32, 52.79 +/- 2.36, 54.68 +/- 1.91, and 59.23 +/- 2.96, there was no significant difference among the groups (F = 5.26, P = 0.19).

CONCLUSIONNec-1, as a specific inhibitor of necroptosis, might effectively block the cell death pathway induced by aluminum, it indicates that necroptosis should be one of the major causes of the SH-SY5Y cell toxicity induced by aluminum, and necroptosis also plays an important role in aluminum induced SH-SY5Y cell death.

Aluminum ; toxicity ; Apoptosis ; drug effects ; Cell Death ; drug effects ; Cell Line, Tumor ; Humans ; Imidazoles ; pharmacology ; Indoles ; pharmacology ; Neuroblastoma

AIMTo study the effect of Na+, K(+)-ATPase inhibition by ouabain on growth and death of vascular endothelial cells ECV304 and involved mechanisms.

METHODSGrowth inhibition of ouabain on ECV304 cells was analyzed using MTT assay. The feature of cell death was studied by Hoechst 33342/PI staining, transmission electron microscopy and DNA agarose gel electrophoresis in ECV304 cells treated with ouabain. The mRNA expression of Na+, K(+)-ATPase alpha1, beta1-subunit was examined by reverse transcription PCR (RT-PCR).

RESULTSOuabain inhibited the growth of ECV304 cells in a dose and time-dependent manner. 10 micromol/L ouabain treated for 24 hours could stimulate the necrosis of ECV304 cells; When treated with 0.1 micromol/L ouabain for 24-48 hours, the cells showed obviously defluxion, the loss of cell-cell contacts, nuclear chromatin condensation, chromatin margination and DNA fragmentation. Na+, K(+)-ATPase alpha1-subunit mRNA expression was significantly up-regulated in ECV304 cells treated with ouabain while the beta1-subunit expression conversely showed a significant decrease.

CONCLUSIONOuabain could up-regulate Na+, K(+)-ATPase alpha1-Subunit expression and reduce beta1-Subunit expression which mediated signal transduction and decreased cell-cell adhesions and induced ECV304 cells death.

Cell Death ; drug effects ; Cell Line ; Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Ouabain ; pharmacology ; Sodium-Potassium-Exchanging ATPase ; metabolism

Lysosomes are degradation and signaling centers within the cell, and their dysfunction impairs a wide variety of cellular processes. To understand the cellular effect of lysosome damage, we screened natural small-molecule compounds that induce lysosomal abnormality using Caenorhabditis elegans (C. elegans) as a model system. A group of vobasinyl-ibogan type bisindole alkaloids (ervachinines A-D) were identified that caused lysosome enlargement in C. elegans macrophage-like cells. Intriguingly, these compounds triggered cell death in the germ line independently of the canonical apoptosis pathway. In mammalian cells, ervachinines A-D induced lysosomal enlargement and damage, leading to leakage of cathepsin proteases, inhibition of autophagosome degradation and necrotic cell death. Further analysis revealed that this ervachinine-induced lysosome damage and lysosomal cell death depended on STAT3 signaling, but not RIP1 or RIP3 signaling. These findings suggest that lysosome-damaging compounds are promising reagents for dissecting signaling mechanisms underlying lysosome homeostasis and lysosome-related human disorders.
Alkaloids ; pharmacology ; Animals ; Caenorhabditis elegans ; cytology ; drug effects ; metabolism ; Cell Death ; drug effects ; Cell Survival ; drug effects ; HeLa Cells ; Humans ; Lysosomes ; drug effects ; pathology ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects

AIMTo study the protective effect of Quinacrine(QA) on rat striatum neurons from the injury caused by heat environment treatment, to probe the relationship between cell membrane injury and cellular injury protection, and to seek the possibility of QA as a preventive agent to heat injury.

METHODSPrimary cultured striatum neurons from newborn rats were pretreated with QA at different concentration for 1 h, and then heat-treated at 43 degrees C for another 1 h. Cell necrosis was detected by Trypan blue staining, and apoptosis was evaluated through Activated Caspase-3 dye and TdT dye.

RESULTSHeat treatment effected the survival of striatum neurons and resulted in great number of cell death, which was mainly mediated by cell necrosis process. It was shown that treatment of QA itself had little effect on the survival of striatum neurons, while QA pretreatment decreased cellular necrosis caused by following heat treatment.

CONCLUSIONQA protects striatum neurons from heat environment injury at about 20 pmol/L, and the protection may mediated by reduction of necrosis.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Death ; drug effects ; Cells, Cultured ; Corpus Striatum ; cytology ; Heat-Shock Response ; Neurons ; drug effects ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVE: To make clear the molecular pathways involved in hydrogen peroxide-induced spiral ganglion cells death. METHOD: The spiral ganglion cells of the newly born rats were primary cultured. Then the SGCs were exposed to hydrogen peroxide for different concentrations (0, 100, 200, 500 micromol/L) and for different hours (2, 4, 6 h). Cell nucleic were stained simultaneously with the DNA binding dyes Hoechst 33258 and propidium iodide. RESULT: At lower concentrations of hydrogen peroxide, apoptosis was the main reason for cell death. At higher concentrations of hydrogen peroxide, the cells died mainly by necrosis. CONCLUSION The effects of hydrogen peroxide are dose and time dependency. Reactive oxygen species may play a role as an early molecule signal in the mechanism of SGCs death.
Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Cell Death ; drug effects ; Cells, Cultured ; Hydrogen Peroxide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spiral Ganglion ; cytology ; drug effects

Amyloid beta (Abeta) neurotoxicity is believed to play a critical role in the pathogenesis of Alzheimer's disease (AD) mainly because of its deposition in AD brain and its neuronal toxicity. However, there have been discrepancies in Abeta-induced cytotoxicity studies, depending on the assay methods. Comparative analysis of Abeta42-induced in vitro cytotoxicity might be useful to elucidate the etiological role of Abeta in the pathogenesis of AD. In this study, MTT, CCK-8, calcein-AM/EthD-1 assays as well as thorough microscopic examinations were comparatively performed after Abeta42 treatment in a neuronal precursor cells (NT2) and a somatic cells (EcR293). Extensive formation of vacuoles was observed at the very early stage of Abeta42 treatment in both cells. Early observation of Abeta42 toxicity as seen in vacuole formation was also shown in MTT assay, but not in CCK-8 and calcein-AM/EthD-1 assays. In addition, Abeta42 treatment dramatically accelerated MTT formazan exocytosis, implying its effect on the extensive formation of cytoplasmic vacuoles. Abeta42 seems to cause indirect inhibition on the intracellular MTT reduction as well as vacuole formation and exocytosis enhancement. Following the acute cellular dysfunction induced by Abeta42, the prolonged treatment of micromolar concentration of Abeta42 resulted in slight inhibition on redox and esterase activity. The early Abeta42-induced vacuolated morphology and later chronic cytotoxic effect in neuronal cell might be linked to the chronic neurodegeneration caused by the accumulation of Abeta42 in AD patients' brain.
Amyloid beta-Protein/*toxicity ; Animals ; Cell Death/drug effects ; Cell Line ; Dose-Response Relationship, Drug ; Exocytosis/*drug effects ; Formazans ; Neurons/*drug effects/metabolism/*pathology ; Peptide Fragments/*toxicity ; Research Support, Non-U.S. Gov't ; Tetrazolium Salts ; Time Factors ; Vacuoles/*drug effects

Biologic scaffold materials composed of extracellular matrix (ECM) are typically obtained in processes that involve decellularization of tissues or organs. Decellularized tissues and organs have been successfully used in a variety of tissue engineering/regenerative medicine applications. Preservation of the complex composition and three-dimensional ultrastructure of the ECM is highly desirable but it is recognized that all methods of decellularization result in disruption of the structure and potential loss of composition. The efficiency of cell removal from a tissue is dependent on the origin of the tissue and the physical, chemical, and enzymatic methods that are used. Each of these treatments affects the biochemical composition, tissue ultrastructure, and mechanical behavior of the remaining ECM scaffold, and all of the treatment methods affect the host response to the material as well. Tissue decellularization with preservation of ECM integrity and bioactivity can be optimized by making correct decisions regarding the agents and techniques utilized during processing. In this paper, the most commonly used decellularization methods are described, and consideration given to the effects of these methods upon the biologic scaffold material and recently described antigen removal strategy are presented.
Acellular Dermis ; Animals ; Cell Death ; drug effects ; Cell Separation ; Extracellular Matrix ; chemistry ; Humans ; Tissue Engineering ; methods ; Tissue Scaffolds

The objective of this study was to investigate the effect of ZnPcH(1)-PDT on the lymphoma cells and its mechanism. Human Burkitt's lymphoma cell line CA46 and mouse lymphoma cell line P388 were selected as objects for study. The killing effect of ZnPcH(1)-PDT on cells were assessed by MTT method and colony formation assay; the cell death patterns were analyzed by AO/EB fluorescence stain, TdT-mediated dUTP nick end labeling (TUNEL), DNA ladder assay; and the different proportions of each death pattern were determined by Annexin-V(-FITC)/PI double stains. The results showed that ZnPcH(1)-PDT displayed anti-proliferation effect on both CA46 cells and P388 cells in dose-dependent manner. CA46 cells were less sensitive to PDT than P388 cells (p < 0.05). Furthermore, PDT could induce cell apoptosis in time-dependent manner. The rate of cell apoptosis increased in the PDT-treated cells. The results of Annexin-V(-FITC)/PI stain indicated that early apoptosis was the main death pattern in the PDT-treated CA46 cells, while early apoptosis and necrosis were the main death model in the PDT-treated P388 cells. It is concluded that ZnPcH(1)-PDT can effectively inhibit lymphoma cell proliferation and induce cell apoptosis.
Animals ; Apoptosis ; drug effects ; Burkitt Lymphoma ; pathology ; therapy ; Cell Death ; drug effects ; Cell Line, Tumor ; Humans ; Mice ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; therapeutic use