[The role of ion channels in apoptosis].
ABSTRACT 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. · 2.15 Impact Factor