Wyniki wyszukiwania - Biblioteka Nauki

1

The role and the function of voltage-gated chloride channels of the ClC family and its defects leading to genetic diseases

100%

Dolowy K. , Bednarczyk P. , Hordejuk R. , Dworakowska B. , Nurowska E. , Jarzabek W.

Postępy Higieny i Medycyny Doświadczalnej

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2002

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tom 56

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nr 3

307-313

EN

There are 9 channels of the ClC family in mammals and few others in fishes, plants, yeast and bacteria. The ClC channels are present in different tissues and play a role in transmembrane potential stabilization, transepithelial transport, cell volume regulation, acidification of intracellular organelles. The genetic defects of ClC-1 chloride channel lead to myotonias, the defect inClC-5 channel to the formation of stones in kidney, while the defect in ClC-Kb channel leads to the Bartter?s syndrome

2

88%

Strosznajder J. , Koladkiewicz I. , Chalimoniuk M. , Samochocki M.

Acta Neurobiologiae Experimentalis

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1998

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tom 58

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nr 2

95-102

EN

The properties of GABA-gated chloride (Cl^-) channels in ischemia-reperfusion injury were studied by determination of the binding and dissociation kinetics of a specific Cl^- channel ligand, tert-butylbicyclophosphoro[^35S]thionate (TBPS) and by determination of ^36Cl^- uptake in the presence of the GABAA receptor agonist, muscimol. Four days after ischemia a small but insignificant decrease of [^35S]TBPS binding to synaptic plasma membranes (SPM) was observed in the hippocampus and cerebral cortex as compared to control. The effect of ischemia was larger and statistically significant after the first and second month of reperfusion, constituting 20% inhibition of [^35S]TBPS binding to SPM of sham-operated gerbils. On the other hand, the half-life of fast phase [^35S]TBPS dissociation four days after ischemia was markedly diminished by about 40%-50% as compared to its control value and persisted during the first and second month of reperfusion in the hippocampal SPM. A similar but less potent reduction of the half-life of the fast phase of [^35S]TBPS dissociation (about 30% versus control) appeared one and two months after ischemia in cerebral cortex SPM. One month after ischemia muscimol-stimulated ^36Cl^- uptake into cerebral cortex synaptoneurosomes was lowered as compared with control uptake, but remained statistically insignificant in the whole range of muscimol concentrations tested. Our results indicated that ischemia-reperfusion injury significantly decreases opening time of GABAA receptor-gated Cl^- channels in the hippocampus and cerebral cortex, which may lower the hyperpolarization ability of this receptor complex leading to an imbalance between excitatory and inhibitory neurotransmitter pathways in these brain areas, and in consequence to neuronal dysfunction or degeneration.

3

Reconstitution of brain mitochondria inner membrane into planar lipid bilayer

75%

Kulawiak B. , Bednarczyk P.

Acta Neurobiologiae Experimentalis

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2005

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tom 65

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nr 3

271-276

EN

Ion channels are present in the inner mitochondrial membrane. They play an important role in cellular processes. Potassium and chloride channels are involved in regulation of mitochondrial volume, membrane potential and acidification. The mitochondrial potassium channels have been suggested as triggers and end effectors in cytoprotection. In our study we measured single channel activities after reconstitution of submitochondrial particles from rat brain mitochondria into planar lipid membranes. After incorporation, two different potassium selective currents were recorded with single channel conductance from 260 to 320 pS and from 70 to 90 pS in gradient (cis/trans) 50/450 and 50/150 mM KC1 solutions, respectively. We also observed activity of the chloride ion channel. The measured single channel conductance was from 80 to 90 pS in gradient {cis/trans) 50/450 mM KC1 solution. Our results suggest that various ion channels are present in the inner mitochondrial membrane of brain mitochondria.

4

Gene therapy perspective in cystic fibrosis

75%

Midro A. T. , Kulczycki L. L. , Sledziewski A.

Postępy Higieny i Medycyny Doświadczalnej

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1993

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tom 47

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nr 4

221-230

EN

(CF) is a frequent autosomal recessive . The isolation of the gene at the CF locus assigned to the long arm of chromosome 7 band q 31 and defining description of its protein named CFTR (cystic fibrosis transmembrane conductance regulator) promoted understanding the basic biochemical defect. Brief review of relevant literature demonstrates that glycoprotein CFTR is a chloride channel and is activated by a combination of phosphorylation by protein kinase a and binding of ATP. Most common mutation of gene, a deletion of the three nucleotides encoding phenylalanine (Delta F508) results in disturbance od chloride transport through membrane of epithelial cells involved in pathomechanism of CF. The way for in CF is open, however therapeutic progress is noted on both pharmacologic arena and on the gene cure front. Recombinant vectors utilizing the adenovirus system with high efficiency of CFTR gene transfer to airway epithelium demonstrated in a rat model look promising. The use of retroviruses for CFTR transfer is also advanced mode of somatic gene therapy. An alternative approach suggesting the use of germ line cells is prerequisite of the development of the preimplantation preconception genetic GF diagnosis. A number of safety and efficacy issues have to be adressed for approaches before human trials can be implemented.