Thioridazine interacts with the membrane of mitochondria acquiring antioxidant activity toward apoptosis--potentially implicated mechanisms.
(65/1081)
We evaluated the effects of the phenothiazine derivative thioridazine on mechanisms of mitochondria potentially implicated in apoptosis, such as those involving reactive oxygen species (ROS) and cytochrome c release, as well as the involvement of drug interaction with mitochondrial membrane in these effects. Within the 0 - 100 microM range thioridazine did not reduce the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) nor did it chelate iron. However, at 10 microM thioridazine showed important antioxidant activity on mitochondria, characterized by inhibition of accumulation of mitochondria-generated O2*-, assayed as lucigenin-derived chemiluminescence, inhibition of Fe2+/citrate-mediated lipid peroxidation of the mitochondrial membrane (LPO), assayed as malondialdehyde generation, and inhibition of Ca2+/t-butyl hydroperoxide (t-BOOH)-induced mitochondrial permeability transition (MPT)/protein-thiol oxidation, assayed as mitochondrial swelling. Thioridazine respectively increased and decreased the fluorescence responses of mitochondria labelled with 1-aniline-8-naphthalene sulfonate (ANS) and 1-(4-trimethylammonium phenyl)-6 phenyl 1,3,5-hexatriene (TMA-DPH). The inhibition of LPO and MPT onset correlated well with the inhibition of cytochrome c release from mitochondria. We conclude that thioridazine interacts with the inner membrane of mitochondria, more likely close to its surface, acquiring antioxidant activity toward processes with potential implications in apoptosis such as O2*- accumulation, as well as LPO, MPT and associated release of cytochrome c. (+info)
Electric and magnetic phenomena observed before the volcano-seismic activity in 2000 in the Izu Island Region, Japan.
(66/1081)
Significant anomalous changes in the ultra low frequency range (approximately 0.01 Hz) were observed in both geoelectric and geomagnetic fields before the major volcano-seismic activity in the Izu Island region, Japan. The spectral intensity of the geoelectric potential difference between some electrodes on Niijima Island and the third principal component of geomagnetic field variations at an array network in Izu Peninsula started to increase from a few months before the onset of the volcano-seismic activity, culminating immediately before nearby magnitude 6 class earthquakes. Appearance of similar changes in two different measurements conducted at two far apart sites seems to provide information supporting the reality of preseismic electromagnetic signals. (+info)
The electric dipole moment of rhodopsin solubilized in Triton X-100.
(67/1081)
The electric dipole moment of solubilized rhodopsin was determined with dielectric dispersion measurements. Rhodopsin was extracted from disc membranes of cattle rod outer segments with the nonionic detergent Triton X-100. The dipole moment of rhodopsin at its isoionic point in the detergent micelle is 720 D (150 charge-A). This value is comparable to dipole moments of nonmembrane proteins, especially those which tend to aggregate or polymerize. Flash irradiation of the rhodopsin results in an increase in the dipole moment of about 25 D (5 charge-A). The light-induced increase in dipole moment appears to be composed of two parts--a faster component related to a change in the number of protons bound by rhodopsin and a slower component apparently independent of the change in proton binding. (+info)
The DC electrical-field-induced Ca(2+) response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation.
(68/1081)
It has been demonstrated that adenosine 5'-triphosphate (ATP) is actively secreted by cells, thereby eliciting Ca(2+)-dependent signal transduction cascades in an autocrine and paracrine manner. In the present study the effects of direct current (DC) electrical fields on ATP release, the intracellular Ca(2+) concentration [Ca(2+)](i) and growth of multicellular prostate tumor spheroids were investigated. Treatment of multicellular tumor spheroids by a single DC electrical field pulse with a field strength of 750 Vm(-1) for 60 seconds resulted in a transient Ca(2+) response, activation of c-Fos and growth stimulation. The initial [Ca(2+)](i) signal was elicited at the anode-facing side of the spheroid and spread with a velocity of approximately 12 microm per second across the spheroid surface. The electrical-field-evoked Ca(2+) response as well as c-Fos activation and growth stimulation of tumor spheroids were inhibited by pretreatment with the anion channel blockers NPPB, niflumic acid and tamoxifen. Furthermore, the Ca(2+) response elicited by electrical field treatment was abolished following purinergic receptor desensitivation by repetitive treatment of tumor spheroids with ATP and pretreatment with the purinergic receptor antagonist suramin as well as with apyrase. Electrical field treatment of tumor spheroids resulted in release of ATP into the supernatant as evaluated by luciferin/luciferase bioluminescence. ATP release was efficiently inhibited in the presence of anion channel blockers. Our data suggest that electrical field treatment of multicellular tumor spheroids results in ATP release, which concomitantly activates purinergic receptors, elicits a Ca(2+) wave spreading through the tumor spheroid tissue and stimulates tumor growth. (+info)
Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats.
(69/1081)
BACKGROUND: The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS) on gastric emptying in the rat. METHODS: GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz) and three pulse amplitudes (5, 20, 40 mA) were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. RESULTS: In both groups, GS increased emptied volumes compared to conditions without stimulation (p < 0.05) for pulse frequencies above 0.5 Hz. Increases in pulse frequencies accelerated gastric emptying (p < 0.01) with a plateau at around 10 Hz. The increase in pulse amplitudes resulted in larger emptied volumes only when the pulse frequency was 1 Hz (p < 0.04) while the opposite effect was observed at 20 Hz (p < 0.04). The most effective combinations to enhance gastric emptying compared to baseline conditions were 10 Hz with 5 or 20 mA. The overall effect of GS on gastric emptying compared to baseline conditions without stimulation, was greater in diabetic than in controls rats (p < 0.05). During stimulation, intragastric pH values were not different from basal conditions during fasting or after a meal in control and diabetic rats. CONCLUSIONS: Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method. (+info)
Electric field effects on red chlorophylls, beta-carotenes and P700 in cyanobacterial Photosystem I complexes.
(70/1081)
We have probed the absorption changes due to an externally applied electric field (Stark effect) of Photosystem I (PSI) core complexes from the cyanobacteria Synechocystis sp. PCC 6803, Synechococcus elongatus and Spirulina platensis. The results reveal that the so-called C719 chlorophylls in S. elongatus and S. platensis are characterized by very large polarizability differences between the ground and electronically excited states (with Tr(Deltaalpha) values up to about 1000 A(3) f(-2)) and by moderately high change in permanent dipole moments (with average Deltamu values between 2 and 3 D f(-1)). The C740 chlorophylls in S. platensis and, in particular, the C708 chlorophylls in all three species give rise to smaller Stark shifts, which are, however, still significantly larger than those found before for monomeric chlorophyll. The results confirm the hypothesis that these states originate from strongly coupled chlorophyll a molecules. The absorption and Stark spectra of the beta-carotene molecules are almost identical in all complexes and suggest similar or slightly higher values for Tr(Deltaalpha) and Deltamu than for those of beta-carotene in solution. Oxidation of P700 did not significantly change the Stark response of the carotenes and the red antenna states C719 and C740, but revealed in all PSI complexes changes around 700-705 and 690-693 nm, which we attribute to the change in permanent dipole moments of reduced P700 and the chlorophylls responsible for the strong absorption band at 690 nm with oxidized P700, respectively. (+info)
Oomycete plant pathogens use electric fields to target roots.
(71/1081)
Plant roots generate electrical currents and associated electrical fields as a consequence of electrogenic ion transport at the root surface. Here we demonstrate that the attraction of swimming zoospores of oomycete plant pathogens to plant roots is mediated in part by electrotaxis in natural root-generated electric fields. The zones of accumulation of anode- or cathode-seeking zoospores adjacent to intact and wounded root surfaces correlated with their in vitro electrotactic behavior. Manipulation of the root electrical field was reflected in changes in the pattern of zoospore accumulation and imposed focal electrical fields were capable of overriding endogenous signals at the root surface. The overall pattern of zoospore accumulation around roots was not affected by the presence of amino acids at concentrations expected within the rhizosphere, although higher concentrations induced encystment and reduced root targeting. The data suggest that electrical signals can augment or override chemical ones in mediating short-range tactic responses of oomycete zoospores at root surfaces. (+info)
Electroreception in juvenile scalloped hammerhead and sandbar sharks.
(72/1081)
The unique head morphology of sphyrnid sharks might have evolved to enhance electrosensory capabilities. The 'enhanced electroreception' hypothesis was tested by comparing the behavioral responses of similarly sized carcharhinid and sphyrnid sharks to prey-simulating electric stimuli. Juvenile scalloped hammerhead sharks Sphyrna lewini and sandbar sharks Carcharhinus plumbeus oriented to dipole electric fields from the same maximum distance (approximately 30 cm) and thus demonstrated comparable behavioral-response thresholds (<1 nV cm(-1)). Despite the similarity of response threshold, the orientation pathways and behaviors differed for the two species. Scalloped hammerheads typically demonstrated a pivot orientation in which the edge of the cephalofoil closest to the dipole remained stationary while the shark bent its trunk to orient to the center of the dipole. By contrast, sandbars swam in a broader arc towards the center of the dipole. The different orientation patterns are attributed to the hydrodynamic properties of the cephalofoil, which enables the hammerheads to execute sharp turns at high speed. The greater trunk width of the sandbar sharks prevented them from demonstrating the same degree of flexibility. Therefore, although the sphyrnid head morphology does not appear to confer a greater sensitivity to prey-simulating dipole electric fields, it does provide (1). a greater lateral search area, which may increase the probability of prey encounter, and (2). enhanced maneuverability, which may aid in prey capture. (+info)