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Cellular calcium homeostasis is controlled predominantly by the plasma membrane calcium pump (PMCA). From four PMCA isoforms, PMCA1 and PMCA4 are ubiquitous, while PMCA2 and PMCA3 are found in excitable cells. We have previously shown that suppression of neuron-specific PMCAs in non-differentiated PC12 cells changed the cell morphology and triggered(More)
Changes in PMCA2 and PMCA3 expression during neuronal development are tightly linked to structural and functional modifications in Ca(2+) handling machinery. Using antisense strategy we obtained stably transfected PC12 lines with reduced level of PMCA2 or PMCA3, which were then subjected to dibutyryl-cAMP differentiation. Reduced level of neuron-specific(More)
Microsomal glutathione transferase 1 (MGST1) possesses glutathione transferase and peroxidase activities and is active in biotransformation of xenobiotics and in defense against oxidative stress. To assess MGST1 role in the development and functioning of PC12 cells, we constructed a cell line with reduced MGST1 (PC12_M). Real-time PCR and immunoblot assays(More)
Plasma membrane Ca(2+)-ATPase (PMCA) by extruding Ca(2+) outside the cell, actively participates in the regulation of intracellular Ca(2+) concentration. Acting as Ca(2+)/H(+) counter-transporter, PMCA transports large quantities of protons which may affect organellar pH homeostasis. PMCA exists in four isoforms (PMCA1-4) but only PMCA2 and PMCA3, due to(More)
A strategy of rationally engineering protein surfaces with the aim of obtaining mutants that are distinctly more susceptible to crystallization than the wild-type protein has previously been suggested. The strategy relies on replacing small clusters of two to three surface residues characterized by high conformational entropy with alanines. This surface(More)
A growing body of evidence indicates that clinical use of ketamine as a promising antidepressant can be accompanied by psychotic-like side effects. Although, the generation of such effects is thought to be attributed to dysfunction of prefrontal GABAergic interneurons, the mechanism underlying ketamine's propsychotic-like action is not fully understood. Due(More)
Chronic N-methyl-D-aspartate receptor (NMDAR) antagonist treatment can provide valuable neurochemical and neuroanatomical models of experimental psychosis. One such antagonist, ketamine, with its short half-time and well-documented psychotomimetic action, has cognitive effects resembling various aspects of schizophrenia-like symptoms. In order to obtain(More)
The DUF1094 family contains over 100 bacterial proteins, all containing a conserved CXC motif, with unknown function. We solved the crystal structure of the Bacillus subtilis representative, the product of the yphP gene. The protein shows remarkable structural similarity to thioredoxins, with a canonical alphabetaalphabetaalphabetabetaalpha topology,(More)
Among hundreds of molecules affecting variety of neuronal processes, neurosteroids form the unique group because of their dual mechanism of action. Classically, they bind to intracellular and/or nuclear receptors, and next modify gene transcription. Another mode of action is linked with the rapid effects induced at the plasma membrane level within seconds(More)
Ketamine, a high affinity uncompetitive antagonist of voltage-dependent NMDA receptor, has been used for years as a dissociative anesthetic. Although the drug is considered as safe and well-tolerable, it is now evident that it can exert dose-dependent multidirectional effects acting on different cellular targets and pathways. The latest clinical studies(More)