[The role of ion channels in apoptosis].
Katedra Termobiologii, Uniwersytet Lódzki, ul. Banacha 12/16, 90-237 Lódź.Postepy biochemii 02/2006; 52(4):373-82.
The plasma membrane as well as the mitochondrial outer and inner membranes contain a number of ion channels that are responsible not only for existence of cells under physiological conditions but they also participate directly in apoptosis. In the apoptotic cells the activated K+, Cl- channels of plasma membrane control the cell volume and mediate the regulation of protease and nuclease activities. The mitochondrial channels are involved in the ionic movements and leakage of apoptogenic factors from the intermembrane space to cytosol. During apoptosis, an important role in the permeabilization of the outer mitochondrial membrane play Bcl-2 family proteins. In this review the recent findings on the function of ion channels in apoptotic cells and the role played by Bcl-2 proteins in the control of apoptosis are discussed.
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ABSTRACT: Remodeling of the pulmonary artery is a major feature of pulmonary artery hypertension, and CPU86017, a derivative of berberine, is known to effectively alleviate hypoxic pulmonary hypertension (HPH). CPU86017 is a racemate, possessing two chiral centers: 7N and 13aC. We have compared the effects of four CPU86017 isomers, SS [(+)-7S, 13aS-CPU86017], SR [(-)-7S, 13aR-CPU86017], RR [(-)-7R, 13aR-CPU86017] and RS [(+)-7R, 13aS-CPU86017], on HPH. Sprague-Dawley rats were exposed to hypoxic conditions (10 +/- 0.5% O2 for 8 h per day) for 4 weeks and treated with CPU86017, SS, SR, RR or RS (4 mg/kg, subcutaneously) from day 15 to 28. After 4 weeks of exposure to hypoxia, remodeling of the right ventricle and the small pulmonary arteries (<150 microm) was very pronounced, and extra-cellular matrix (ECM) had been excessively produced in association with abnormal mRNA and protein expression of matrix metalloproteinase 9 (MMP9) and mRNA of tissue inhibitor of matrix metalloproteinase 1 and 2 (TIMP1, TIMP2). Expression of endothelin receptor A was upregulated, while that connexin 40 was downregulated. The administration of CPU86017 and its four isomers attenuated the changes, with the isomer RS exhibiting the most favorable effect on HPH rats. We propose that an activated endothelin pathway associated with an unbalanced MMP-TIMP system may contribute to the over-accumulation of ECM and the remodeling of the pulmonary arterioles in HPH. CPU86017 and its four isomers attenuate ECM accumulation and vascular remodeling by normalizing both the MMP-TIMP system and the ET system. The RS isomer is superior to the racemate CPU86017 in attenuating HPH.Archiv für Experimentelle Pathologie und Pharmakologie 06/2008; 378(5):541-52. DOI:10.1007/s00210-008-0309-4 · 2.47 Impact Factor
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ABSTRACT: Defect-free polymeric dual-layer hollow fiber membranes consisting of an ultrathin dense-selective polyamide imide (PAI) layer and a polyethersulfone (PES) supporting layer have been successfully fabricated in this study for gas separation application. It is observed that a lower outer-layer dope flow rate does not necessarily result in the formation of an ultrathin dense-selective layer upon the PES supporting layer. An optimization in the velocity between the inner-layer and the outer-layer dopes at the exit of the spinneret is essential to minimize additional stresses and defect formation in the outer functional layer. The best gas separation performance of the PAI–PES dual-layer hollow fibers fabricated in this study has an O2/N2 selectivity of 7.73 with a dense-selective layer thickness of 63 nm. Positron annihilation spectroscopy (PAS) has been used for the first time to explore the morphology and predict the gas separation performance of PAI–PES based dual-layer hollow fiber membranes. Doppler broadening energy spectra (DBES) from PAS accurately estimate the outer-layer thickness and demonstrate the existence of the multilayered structure of the dual-layer hollow fiber membranes. Besides, the PAS fitted data reveal that the fiber spun under the optimal condition has the densest selective layer, which agrees well with the highest gas-pair selectivity observed under this condition.Highlights► Defect-free dual-layer hollow fiber membranes with ultrathin dense-selective layer. ► O2/N2 selectivity of 7.73 with a dense-selective layer thickness of 63 nm. ► PAS to explore the morphology and predict the gas performance. ► PAS estimate the outer-layer thickness and demonstrate the layered structure. ► PAS fitted data agrees well with the experimental result.Journal of Membrane Science 08/2011; 378(1-2):541-550. DOI:10.1016/j.memsci.2011.05.048 · 5.06 Impact Factor