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It is well known that the terpenoid ferutinin (4-oxy-6-(4-oxybenzoyloxy) dauc-8,9-en), isolated from the plant Ferula tenuisecta, considerably increases the permeability of artificial and cellular membranes to Ca2+-ions and produces apoptotic cell death in different cell lines in a mitochondria-dependent manner. The present study was designed for further evaluation of the mechanism(s) of mitochondrial effects of ferutinin using isolated rat liver mitochondria. Our findings provide evidence for ferutinin at concentrations of 5-27 µM to decrease state 3 respiration and the acceptor control ratio in the case of glutamate/malate as substrates. Ferutinin alone (10-60 µM) also dose-dependently dissipated membrane potential. In the presence of Ca2+-ions, ferutinin (10-60 µM) induced considerable depolarization of the inner mitochondrial membrane, which was partially inhibited by EGTA, and permeability transition pore formation, which was diminished partly by cyclosporin A, and did not influence markedly the effect of Ca2+ on mitochondrial respiration. Ruthenium Red, a specific inhibitor of mitochondrial calcium uniporter, completely inhibited Ca2+-induced mitochondria swelling and membrane depolarization, but did not affect markedly the stimulation of these Ca2+-dependent processes by ferutinin. We concluded that the mitochondrial effects of ferutinin might be primarily induced by stimulation of mitochondrial membrane Ca2+-permeability, but other mechanisms, such as driving of univalent cations, might be involved. [ABSTRACT FROM AUTHOR]

To investigate the molecular interaction of amyloid beta peptides Aβ1–28 or Aβ25–40 with model lipid membranes differential scanning calorimetry (DSC) and DPH and TMA DPH fluorescence anisotropy approaches were used. The main transition temperature ( Tm) and enthalpy change (Δ H) of model lipid membranes composed of DMPC/DPPG on addition of Aβ25–40 or Aβ25–40 at 10:1 (w/w) phospholipid/peptide ratio either non-aggregated or previously aggregated were examined. The effect of Aβ1–28 and Aβ25–40 on the membrane fluidity of liposomes made of DMPC/DPPG (98:2 w/w) was determined by fluorescence anisotropy of incorporated DPH and TMA DPH. The results of this study provide information that Aβ1–28 preferentially interacts with the hydrophilic part of the model membranes, while Aβ25–40 rather locates itself in the hydrophobic core of the bilayer where it reduces the order of the phospholipids packing. [ABSTRACT FROM AUTHOR]

Abstract: It was previously shown that cells die with increased cytosolic ATP after stimulation with apoptotic inducers including staurosporine (STS). To identify the source of apoptotic ATP elevation, we monitored, in real time, the cytosolic ATP level in luciferase-expressing HeLa cells. A mitochondrial uncoupler or a respiration chain inhibitor was found to decrease cytosolic ATP by about 50%. However, even when mitochondrial ATP synthesis was suppressed, STS induced a profound elevation of intracellular ATP. In contrast, the STS-induced ATP increase was prevented by any of three inhibitors of the glycolytic pathway: 2-deoxyglucose, iodoacetamide, and NaF. The STS effect strongly depended on intracellular calcium and was mimicked by a calcium ionophore. We conclude that Ca2+-dependent activation of anaerobic glycolysis, but not aerobic mitochondrial oxidative phosphorylation, is responsible for the STS-induced elevation of ATP in apoptotic HeLa cells. [Copyright &y& Elsevier]

Several studies reported that bisphenol A (BPA) and its metabolite hydroquinone (HQ) have adverse effects on human and animal health. In this work, a comparative study of influence of the BPA and HQ, environment pollutants, on human erythrocytes was carried out. It was shown that BPA and HQ to varying extents caused oxidative damage in human erythrocytes: hemolysis, decreased GSH level, and methemoglobin formation. It was demonstrated that hydrolysable tannins 3,6-bis-O-di-O-galloyl-1,2,4-tri-O-galloyl-β-D-glucose (C 55 H 40 O 34 ) and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (C 41 H 32 O 26 ) (PGG) isolated from the Rhus typhina L. leaves in the range of 1-50 μM concentrations inhibited hemolysis and methemoglobin formation and also increased intracellular reduced glutathione in erythrocytes treated with BPA or HQ. It was revealed by electron paramagnetic resonance (EPR) using 5-doxyl-stearic acid (5-DS) that C 55 H 40 O 34 and C 41 H 32 O 26 increased the rigidity of erythrocyte membranes at the depth of 5th carbon atom of the fatty acid hydrocarbon chain. Taken together, these results allow to conclude that tannins from the Rhus typhina L. leaves protect erythrocytes from oxidative stress caused by BPA or HQ both due to their antioxidant activity as well as their interaction with the erythrocyte membrane components.

Background: Silibinin, a naturally-occurring flavonoid produced by milk thistle, possesses antioxidant, anti-inflammatory and cancer-preventive activities. In the current study, we examined the effects of silibinin on the expression of secreted phospholipase A2 (sPLA2) enzymes, especially those of group IIA (hGIIA), which play a crucial role in inflammation and carcinogenesis., Materials and Methods: The effects of silibinin on sPLA2 expressions in human HepG2 hepatoma and PC-3 prostate cancer cells were analyzed using quantitative reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay technique., Results: Silibinin inhibited the expression of hGIIA in unstimulated and cytokine-primed HepG2 and PC-3 cells. The mRNA levels of sPLA2 of groups IB, III and V were also significantly decreased by silibinin. Analyses of transcription factor activation suggest that nuclear factor-κB, but not specificity protein 1 (SP1) is implicated in the silibinin-mediated down-regulation of hGIIA., Conclusion: Silibinin exhibits inhibitory effects on basal and cytokine-induced expression of sPLA2s in cancer cells and therefore, may have the potential to protect against up-regulation of hGIIA and other sPLA2 isoforms during inflammation and cancer.