This review is focused on ankyrin which is a protein linker between the integral membrane proteins and spectrinbased cytoskeleton. Structure and distribution of different ankyrin isoforms that are products of alternative-spliced genes are described. Interaction of ankyrins with various membranes is considered. Special attention is paid to ankyrin participation in signal transduction and in assembly of integral membrane proteins in specialized membrane domains. ß
It is shown that histidine-containing dipeptide carnosine (beta-alanyl-L-histidine), which is present in skeletal muscles in millimolar concentrations, decreases the rate of Ca2+ accumulation by the heavy fraction of sarcoplasmic reticulum from rabbit skeletal muscles. This effect results from the ability of carnosine to induce a rapid Ca2+ release from the heavy sarcoplasmic reticulum vesicles via activation of the ruthenium red-sensitive Ca-channels. The effect of carnosine is dose-dependent that indicates the presence of saturable site(s) for carnosine in the molecules of Ca-channels. The C0.5 value carnosine (the concentration that induces the half-maximal Ca2+ release) is 8.7 mM. The 1 N-methylated derivative of carnosine, i.e., anserine, also induces a rapid Ca2+ release with the half-maximal effect at 2.7 mM. Conversely, neither histidine nor beta-alanine (both separately and in the mixture) cause Ca2+ release. In addition, carnosine increases the sensitivity of Ca-channels to their well-known activators (caffeine, AMP, and Ca2+) and decreases inhibitory effect of low concentrations of Mg2+. It is concluded that carnosine as a component of skeletal muscles can be an endogenous regulator of the sarcoplasmic reticulum Ca-channel activity.
Recent studies demonstrate that cytotoxic actions of ouabain and other cardiotonic steroids (CTS) on renal epithelial cells (REC) are triggered by their interaction with the Na(+),K(+)-ATPase alpha-subunit but not the result of inhibition of Na(+),K(+)-ATPase-mediated ion fluxes and inversion of the [Na(+)](i)/[K(+)](i) ratio. This study examined the role of mitogen-activated protein kinases (MAPK) in the death of ouabain-treated REC. Exposure of C7-MDCK cells that resembled principal cells from canine kidney to 3 microM ouabain led to phosphorylation of p38 without significant impact on phosphorylation of ERK and JNK MAPK. Maximal increment of p38 phosphorylation was observed at 4 h followed by cell death at 12 h of ouabain addition. In contrast to ouabain, neither cell death nor p38 MAPK phosphorylation were affected by elevation of the [Na(+)](i)/[K(+)](i) ratio triggered by Na(+),K(+)-ATPase inhibition in K(+)-free medium. p38 phosphorylation was noted in all other cell types exhibiting death in the presence of ouabain, such as intercalated cells from canine kidney and human colon rectal carcinoma cells. We did not observe any action of ouabain on p38 phosphorylation in ouabain-resistant smooth muscle cells from rat aorta and endothelial cells from human umbilical vein. Both p38 phosphorylation and death of ouabain-treated C7-MDCK cells were suppressed by p38 inhibitor SB 202190 but were resistant to its inactive analogue SB 202474. Our results demonstrate that death of CTS-treated REC is triggered by Na (i) (+) ,K (i) (+) -independent activation of p38 MAPK.
It is known that the light fraction of rabbit skeletal muscle sarcoplasmic reticulum vesicles can release Ca2+ from the intravesicular space, although the Ca2+-conductive channels are present only in the heavy fraction of sarcoplasmic reticulum vesicles. To study the possible pathways of the Ca2+ leakage from light vesicles we have used a short-term treatment for 4.5 min at 45°C which quickly decreases the efficiency of Ca2+-transporting ATPase operation without any visible effects on the hydrolytic activity of the Ca2+-ATPase in the membranes. The treatment of the vesicles decreased the negative membrane surface potential created by the Ca2+-ATPase. Comparative titration of control and heat-treated preparations of light sarcoplasmic reticulum vesicles by K+, Na+, Mg2+, and Ca2+ revealed clear differences in their surface properties. The short-term heating resulted in release of Ca2+ from the vesicles previously loaded with 45Ca2+, which indicates an increase in passive membrane permeability to Ca2+. Study of Ca2+-ATPase protein arrangement in the membrane indicated that the heat treatment induced protein oligomerization and some of the Ca2+-ATPase molecules acquired intermolecular and intramolecular covalent bonds. From these data, we have concluded that the changes in the surface and structure properties of the vesicle membranes after the short-term heat treatment were the result of clustering of the CaZ+-ATPase molecules. This protein rearrangement may create channels for calcium leakage from light sarcoplasmic reticulum vesicles.The sarcoplasmic reticulum (SR) plays a key role in excitation-contraction coupling between nerve impulses and muscle contraction. The skeletal muscle SR consists of two morphologically and functionally distinct regions, namely the lateral sacs (heavy fraction of vesicles after centrifugation in a sucrose density gradient) and the longitudinal tubules (light fraction of vesicles) which differ in protein composition [l]. The lateral sacs contain Ca2+ channels and provide fast release of stored Ca2+ [l, 21. The role of the longitudinal tubules, which are rich in CaZ+-ATPase protein, is calcium accumulation. The latter process involves active transport in which Ca" translocation is coupled with ATP hydrolysis [3]. It is known that short-term heating of SR vesicles at 42-45 "C leads to a quick decrease of Ca2+-transporting ATPase (Ca'+ pump) efficiency without an effect on the Ca2+-ATPase hydrolytic activity [4, 53. Studying the mechanism of the Ca2+ pump thermal uncoupling may be useful for understanding the possible pathways of Ca" release from SR. New pathways for Caz+ release from SR could be found which may be relevant to the regulation of the Caz+ exchange in muscle tissue under normal and pathological conditions. It has been shown that the decrease in the Ca2+ transport efficiency upon short-term heating of SR vesicles was not connected with true intramolecular uncoupling of Ca2+ pump [6]. To evaluate conformational changes of the Caz+-ATPase after heat treatment, kinetic paramete...
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