AChE and the amyloid precursor protein (APP) - Cross-talk in Alzheimer's disease.

The amyloid precursor protein (APP) and acetylcholinesterase (AChE) are multi-faceted proteins with a wide range of vital functions, both crucially linked with the pathogenesis of Alzheimer's disease (AD). APP is the precursor of the Aβ peptide, the pathological agent in AD, while AChE is linked to its pathogenesis either by increasing cholinergic deficit or exacerbating Aβ fibril formation and toxicity. As such, both proteins are the main targets in AD therapeutics with AChE inhibitors being currently the only clinically available AD drugs.

GM1 ganglioside activates ERK1/2 and Akt downstream of Trk tyrosine kinase and protects PC12 cells against hydrogen peroxide toxicity.

Ganglioside GM1 at micro- and nanomolar concentrations was shown to increase the viability of pheochromocytoma PC12 cells exposed to hydrogen peroxide and diminish the accumulation of reactive oxygen species and oxidative inactivation of Na(+),K(+)-ATPase, the effects of micromolar GM1 being more pronounced than those of nanomolar GM1. These effects of GM1 were abolished by Trk receptor tyrosine kinase inhibitor and diminished by MEK1/2, phosphoinositide 3-kinase and protein kinase C inhibitors. Hydrogen peroxide activates Trk tyrosine kinase; Akt and ERK1/2 are activated downstream of this protein kinase.

Mitochondrial electron transport chain in heavy metal-induced neurotoxicity: effects of cadmium, mercury, and copper.

To clarify the role of mitochondrial electron transport chain (mtETC) in heavy-metal-induced neurotoxicity, we studied action of Cd(2+), Hg(2+), and Cu(2+) on cell viability, intracellular reactive oxygen species formation, respiratory function, and mitochondrial membrane potential of rat cell line PC12. As found, the metals produced, although in a different way, dose- and time-dependent changes of all these parameters. Importantly, Cd(2+) beginning from 10 [mu]M and already at short incubation time (3 h) significantly inhibited the FCCP-uncoupled cell respiration; besides, practically the complete inhibition of the respiration was reached after 3 h incubation with 50 [mu]M Hg(2+) or 500 [mu]M Cd(2+), whereas even after 48 h exposure with 500 [mu]M Cu(2+), only a 50% inhibition of the respiration occurred.

Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer's disease?

: The amyloid cascade hypothesis of Alzheimer's disease envisages that the initial elevation of amyloid β-peptide (Aβ) levels, especially of Aβ(1-42) , is the primary trigger for the neuronal cell death specific to onset of Alzheimer's disease. There is now substantial evidence that brain amyloid levels are manipulable because of a dynamic equilibrium between their synthesis from the amyloid precursor protein and their removal by amyloid-degrading enzymes (ADEs) providing a potential therapeutic strategy. Since the initial reports over a decade ago that two zinc metallopeptidases, insulin-degrading enzyme and neprilysin (NEP), contributed to amyloid degradation in the brain, there is now an embarras de richesses in relation to this category of enzymes, which currently number almost 20.

Mechanism(s) of Toxic Action of Zn and Selenite: A Study on AS-30D Hepatoma Cells and Isolated Mitochondria.

Mitochondria of AS-30D rat ascites hepatoma cells are found to be the main target for Zn(2+) and sodium selenite (Na(2)SeO(3)). High [mu]M concentrations of Zn(2+) or selenite were strongly cytotoxic, killing the AS-30D cells by both apoptotic and necrotic ways. Both Zn(2+) and selenite produced strong changes in intracellular generation of reactive oxygen species (ROS) and the mitochondrial dysfunction via the mitochondrial electron transport chain (mtETC) disturbance, the membrane potential dissipation, and the mitochondrial permeability transition pore opening.

Tubular GFP uptake pattern in the rat and frog kidneys.

The renal tubular uptake of green fluorescent protein (GFP) after its bolus intravenous injection was studied in both frogs and rats. GFP fluorescence in the proximal tubule (PT) was revealed by fluorescent and confocal microscopy. Granular GFP fluorescence was observed nearby in the apical membrane of PT cells featuring distribution over the cytoplasm.

Behavior of toads, Bufo bufo, in a dynamic environment.

Susceptibility to motion sickness was tested by exposing free moving toads to rotation of a stimulator modeled after an amusement park Ferris Wheel. The stimulator provided a gentle stimulation of frequency 0.25 Hz and centrifugal acceleration 0.

Fish otolith asymmetry: morphometry and modeling.

Mathematical modeling suggests that relatively large values of otolith mass asymmetry in fishes can alter acoustic functionality and may be responsible for abnormal fish behavior when subjected to weightlessness during parabolic or space flight [D.V. Lychakov, Y.

Fish otolith mass asymmetry: morphometry and influence on acoustic functionality.

The role of the fish otolith mass asymmetry in acoustic functionality is studied. The saccular, lagenar and utricular otoliths are weighted in two species of the Black Sea rays, 15 species of the Black Sea teleost fish and guppy fish. The dimensionless otolith mass asymmetry chi is calculated as ratio of the difference between masses of the right and left paired otoliths to average otolith mass.

N1-acetyl-N2-formyl-5-methoxykynuramine is a product of melatonin oxidation in rats.

The product of melatonin oxidation, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), was synthesized and a method for its determination in biological samples was developed. High performance liquid chromatography (HPLC) with fluorescence detection provided good sensitivity and selectivity. Wavelengths of 350 and 480 nm were used for excitation and emission, respectively.

Modulation of the effect of arginine-vasopressin on water and ion transport in the newt early distal tubule and frog urinary bladder by V1-antagonists.

In the early distal tubule of the newt Triturus vulgaris L., 1 nM arginine-vasopressin (AVP) increased water reabsorption; the fractional reabsorption of Na+ was elevated from 46.2 +/- 6.