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PubMed1998

Transport of free polymannose-type oligosaccharides from the endoplasmic reticulum into the cytosol is inhibited by mannosides and requires a thapsigargin-sensitive calcium store.

The transport of free polymannose-type oligosaccharides from the lumen of the endoplasmic reticulum into the cytosol has been recently demonstrated (Moore,S.E.H., et al., 1995, EMBO J., 14, 6034-6042), but at present little is known of the characteristics of this process. Here, it is shown that inhibition of the transport of endogenously synthesized metabolically radiolabeled free oligosaccharides out of the endoplasmic reticulum into the cytosol of permeabilized HepG2 cells occurs when assays are conducted in the presence of mannose (IC50, 4.9 mM), or its derivatives modified at the first carbon (C1) of the sugar ring; alpha-methyl mannoside (IC50, 2.0 mM), mannoheptulose (IC50, 1.6 mM), and alpha-benzyl mannoside (IC50, 0.8 mM), whereas other monosaccharides (50 mM), differing from mannose at position; C2 (glucose), C3 (altrose), C4 (talose), C5 (l-rhamnose), and C6 (mannoheptose), have little effect. N-Acetylglucosamine does not inhibit oligosaccharide transport and, furthermore, although mannobioses and a mannotriose inhibit free oligosaccharide transport, di-N-acetylchitobiose is without effect. It is also shown that if the transport assay buffer is either depleted of calcium ions, or supplemented with the Ca2+/Mg2+ATPase inhibitor, thapsigargin, or with calcium ionophores, free oligosaccharide transport out of the endoplasmic reticulum is inhibited. These results demonstrate that the terminal nonreducing mannosyl residues of free polymannose-type oligosaccharides and not their N-acetylglucosamine-containing reducing termini, play an important role in the interaction of the free oligosaccharide with the transport machinery, and that this transport process requires the presence of calcium sequestered in the lumen of the endoplasmic reticulum.

Adenosine Triphosphate↗
PubMed1997

Induction of calcium release from isolated sarcoplasmic reticulum by triphenyltin.

A direct peripheral myopathy has been found in organotin intoxication and suggested to be a significant factor in the development of muscle weakness following exposure. In this study, by using the isolated sarcoplasmic reticulum membrane vesicles, we have shown that triphenyltin dose-dependently induced Ca2+ release from the actively and passively loaded sarcoplasmic reticulum vesicles. Triphenyltin induced Ca2+ release in ruthenium red-sensitive and insensitive ways with EC50 values of 75 and 270 microM, respectively. The Ca2+-ATPase activity and Ca2+ uptake of sarcoplasmic reticulum were also inhibited by triphenyltin. Triphenyltin exerted dual effects on the apparent [3H]ryanodine binding. Triphenyltin (0.5-10 microM) dose-dependently potentiated the [3H]ryanodine binding; however, the [3H]ryanodine binding decreased as the concentration of triphenyltin increased. The dissociation of bound [3H]ryanodine was facilitated by triphenyltin. The present study suggested that the internal Ca2+ store of skeletal muscle could be depleted by triphenyltin through the inhibition of the Ca2+ uptake and the induction of Ca2+ release by acting on the Ca2+-ATPase and Ca2+ release channel, also known as the ryanodine receptor, of sarcoplasmic reticulum, respectively. These results could partly explain the development of muscle weakness in organotin intoxication; however, their relevance to the development of peripheral myopathy requires further examination.

Animals↗
PubMed1995

Subcellular targeting of the endoplasmic reticulum and plasma membrane Ca2+ pumps: a study using recombinant chimeras.

ATP-powered Ca2+ pumps are located in the plasma membrane (PMCA) and the sarco(endo)plasmic reticulum (SERCA). The two pump types share numerous structural and functional features; nevertheless, they are strictly targeted to different cell compartments. Chimeric SERCA/PMCA pumps were constructed to investigate the structural determinants responsible for their specific cellular location. The level of expression of the chimeric constructs and of the wild-type pumps in COS-7 and Sf9 cells was the same and so was their stability. One exception was chimera D, which showed special propensity to degradation. The chimeric constructs had no Ca(2+)-dependent ATPase activity, although in one trace amounts of the Ca(2+)-dependent phosphoenzyme intermediate were detected. Thus, the exchange of the regions encompassing the (NH2-terminal) transmembrane domains apparently is incompatible with the activity of the pump. The immunofluorescence experiments showed that the 85 NH2-terminal residues of the SERCA pump, encompassing the first transmembrane domain, contain a signal-promoting retention of chimeric constructs otherwise consisting of the PMCA pump structure in the endoplasmic reticulum. Additional structural determinants most likely also contribute to the retention of the SERCA pump in the endoplasmic reticulum: one chimeric construct (E) composed of the first two transmembrane domains of the PMCA pump, followed by the remainder of the SERCA pump structure, was still retained, even if not completely, in the endoplasmic reticulum.

Animals↗
PubMed1994

Effect of thiopental on Ca2+ release from sarcoplasmic reticulum in intact myocardium.

BACKGROUND: While thiopental is known to inhibit the myocardial transsarcolemmal influx of Ca2+, the effect of thiopental on sarcoplasmic reticular Ca2+ release has not been characterized. METHODS: Isolated papillary muscles of rabbits were used. We measured postrest contractions to assess the Ca2+ release by sarcoplasmic reticulum in response to electrical stimulation. Contractures induced by rapid cooling were used as an index of Ca2+ content of sarcoplasmic reticulum. The effect of thiopental on the availability of extracellularly derived Ca2+ was evaluated from measurements of contractions at 0.1 Hz in the presence of 1 microM ryanodine. RESULTS: Thiopental sodium (10, 20, and 30 mg/l; 38, 76, and 113 microM) inhibited the postrest contraction but not the contracture induced by rapid cooling. In the presence ryanodine, thiopental inhibited the postrest contraction elicited after 10 s of rest after 2-Hz stimulation much less than the steady-state contraction at 0.1 Hz (beat interval 10 s). Thiopental inhibited the postrest contraction (no ryanodine present) more strongly than did Ni2+ (an inhibitor of the transsarcolemmal Ca2+ influx) when the contraction at 0.1 Hz in the presence of ryanodine was inhibited to the same extent. CONCLUSIONS: These results suggest that thiopental decreases sarcoplasmic reticulum Ca2+ release induced by electrical stimulation and inhibits the ryanodine-induced efflux of sarcoplasmic reticulum Ca2+.

Animals↗
PubMed1999

Interaction of bupivacaine and tetracaine with the sarcoplasmic reticulum Ca2+ release channel of skeletal and cardiac muscles.

BACKGROUND: Although various local anesthetics can cause histologic damage to skeletal muscle when injected intramuscularly, bupivacaine appears to have an exceptionally high rate of myotoxicity. Research has suggested that an effect of bupivacaine on sarcoplasmic reticulum Ca2+ release is involved in its myotoxicity, but direct evidence is lacking. Furthermore, it is not known whether the toxicity depends on the unique chemical characteristics of bupivacaine and whether the toxicity is found only in skeletal muscle. METHODS: The authors studied the effects of bupivacaine and the similarly lipid-soluble local anesthetic, tetracaine, on the Ca2+ release channel-ryanodine receptor of sarcoplasmic reticulum in swine skeletal and cardiac muscle. [3H]Ryanodine binding was used to measure the activity of the Ca2+ release channel-ryanodine receptors in microsomes of both muscles. RESULTS: Bupivacaine enhanced (by two times at 5 mM) and inhibited (66% inhibition at 10 mM) [3H]ryanodine binding to skeletal muscle microsomes. In contrast, only inhibitory effects were observed with cardiac microsomes (about 3 mM for half-maximal inhibition). Tetracaine, which inhibits [3H]ryanodine binding to skeletal muscle microsomes, also inhibited [3H]ryanodine binding to cardiac muscle microsomes (half-maximal inhibition at 99 microM). CONCLUSIONS: Bupivacaine's ability to enhance Ca2+ release channel-ryanodine receptor activity of skeletal muscle sarcoplasmic reticulum most likely contributes to the myotoxicity of this local anesthetic. Thus, the pronounced myotoxicity of bupivacaine may be the result of this specific effect on Ca2+ release channel-ryanodine receptor superimposed on a nonspecific action on lipid bilayers to increase the Ca2+ permeability of sarcoplasmic reticulum membranes, an effect shared by all local anesthetics. The specific action of tetracaine to inhibit Ca2+ release channel-ryanodine receptor activity may in part counterbalance the nonspecific action, resulting in moderate myotoxicity.

Anesthetics, Local↗
PubMed2000

Propofol-induced modifications of cardiomyocyte calcium transient and sarcoplasmic reticulum function in rats.

BACKGROUND: Propofol is considered to be an anesthetic agent with few or no negative inotropic effects. This study evaluated a possible direct depressant effect of propofol on sarcoplasmic reticulum Ca2+ accumulation and cardiomyocytes. METHODS: The effects of propofol on intracellular Ca2+ transients were evaluated in isolated rat cardiomyocytes using a microfluorometric technique with Indo-1. Sarcoplasmic reticulum function was also assessed by measuring the oxalate-stimulated Ca2+ uptake from homogenates of rat ventricles. RESULTS: The Ca2+ uptake capacity of the sarcoplasmic reticulum was decreased by propofol (10(-4) M). Large concentrations of propofol decreased the rate of decrease of the intracellular Ca2+ transient, which resulted in an increase of diastolic Ca2+ when the diastolic interval was decreased. The increased diastolic Ca2+ also resulted in a decrease in Ca2+ transient. This effect appeared for lower doses (10(-5) M) after a short diastolic pause rather than after a long (2- to 3-min) rest (appearing at 10(-4) M). CONCLUSIONS: For doses more than 10(-5) M, propofol induces a Ca2+ uptake capacity impairment of the sarcoplasmic reticulum. This is probably responsible for a slowing of the decrease of the Ca2+ transient, which in turn increases the diastolic Ca2+ for high heart rate. These diastolic modifications may participate in the slight negative inotropic effect of the drug.

Anesthetics, Intravenous↗
PubMed1990

Intestinal calcium transport in spontaneously hypertensive rats and their genetically matched Wistar-Kyoto rats. I. Endoplasmic reticulum.

The present study was designed to investigate calcium uptake by the intestinal endoplasmic reticulum in the spontaneously hypertensive rat (SHR) and its genetically matched normotensive control, the Wistar-Kyoto rat (WKY). The calcium uptake was characterized before (weanling) and after (adult) development of hypertension in SHR and their age-matched WKY controls. Adenosine 5'-triphosphate (ATP)-driven calcium uptake with time was stimulated several-fold compared with the no-ATP condition, and the maximal uptake occurred after 15 min in both SHR and WKY. The maximal ATP-dependent calcium uptake was significantly greater in the intestinal endoplasmic reticulum of adult SHR than in that of WKY (P less than 0.05). The initial rate of calcium uptake was linear up to 30 s in both SHR and WKY. The kinetics of ATP-dependent calcium uptake at a concentration between 0.1 and 1.0 mumol/l showed a maximal uptake (Vmax) of 1.89 +/- 0.3 and 1.06 +/- 0.1 nmol/mg protein per 15 s for adult SHR and WKY, respectively (P less than 0.02), and binding constant (Km) values of 0.15 +/- 0.08 and 0.12 +/- 0.05 mumol/l, respectively. The ontogeny of calcium uptake by intestinal endoplasmic reticulum was characterized before the development of hypertension in weanling (3-week-old) SHR and WKY. In both SHR and WKY weanlings, calcium uptake by the intestinal endoplasmic reticulum was enhanced several-fold by the presence of ATP compared with the no-ATP condition, and the maximal uptake occurred after 15 min. The maximal ATP-dependent calcium uptake was significantly greater in 3-week-old SHR than in age-matched WKY (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Malfunction of arterial sarcoplasmic reticulum leading to faster and greater contraction induced by high-potassium depolarization in young spontaneously hypertensive rats.

The contribution of sarcoplasmic reticulum was studied with regard to the increase in arterial contraction induced by a high-potassium depolarization in spontaneously hypertensive rats (SHR). The 20 mmol/l potassium-induced contraction of femoral arteries was faster and greater in 6-week-old SHR than in age-matched normotensive Wistar-Kyoto (WKY) rats. Relaxation after washing the arteries with a Krebs solution was slower in SHR than in WKY rats. When the sarcoplasmic reticulum of SHR arteries had been depleted of calcium by caffeine in a calcium-free solution, the rate of high-potassium-induced contraction of the calcium-depleted SHR arteries was slowed, the same result as that with non-calcium-depleted WKY arteries. In ryanodine-treated arteries, the rate and magnitude of high-potassium-induced contraction were enhanced slightly in SHR and greatly in WKY rats, resulting in no final difference between SHR and WKY rats. Ryanodine slowed the relaxation rate in WKY rats but not in SHR. These results suggest that the diminution in ability of sarcoplasmic reticulum to sequester calcium may be responsible for the faster rate and greater magnitude of high-potassium-induced contraction with the slower relaxation in SHR arteries. We postulated that genetic malfunction of sarcoplasmic reticulum causes the increased contraction of arterial smooth muscle leading to the enhanced vasoconstriction and elevated blood pressure in SHR.

Animals↗
PubMedDate not supplied

Effects of propranolol and timolol on calcium uptake by sarcoplasmic reticulum vesicles.

The effects of the beta-adrenergic receptor blocking agents propranolol and timolol on the initial calcium uptake velocity of sarcoplasmic reticulum vesicles of rabbit skeletal muscle were studied. Racemic d- and l-propranolol had similar inhibitory effects on initial calcium uptake velocity, which was inhibited 50% by 5--7 X 10(-4) M racemic propranolol. Timolol was a much less potent inhibitor of initial calcim uptake velocity; 50% inhibition occurred at approximately 10(-2) M timolol. Both drugs inhibited maximal calcium uptake velocity; however, KCa (the Ca2+ concentration at which calcium uptake was half-maximal) was modified differently. Propranolol increased KCa, whereas timolol caused the KCa to decrease. Addition of either drug to an ongoing calcium uptake reaction at the time that calcium content became maximal caused renewed calcium uptake. The relative potencies of propranolol and timolol as negative inotropic agents are similar to their potencies as inhibitors of sarcoplasmic reticulum calcium uptake, but dissimilar to their beta-adrenergic receptor blocking potencies. Timolol, which has been reported to have less negative inotropic effect than propranolol, is approximately 5 time more potent than propranolol as a beta-adrenergic receptor blocking agent but 15 times less potent as an inhibitor of sarcoplasmic reticulum calcium uptake. Inhibition of sarcoplasmic reticulum calcium uptake may thus characterize negative inotropic potencies of new beta-adrenergic receptor blocking agents.

Animals↗
PubMedDate not supplied

Abnormal tubular structures associated with the granular endoplasmic reticulum of neocortical neurons in a biopsy from a patient with Alzheimer's disease.

The electron microscope has been used to examine a diagnostic biopsy of frontal neocortex which showed the light microscopic features of Alzheimer's disease. In addition to plaques and tangles, the biopsy showed some neurons which contained abnormal tubular profiles specifically associated with their granular endoplasmic reticulum. In transverse section the profiles consisted of two concentric layers of trilaminar unit membrane with an overall diameter of approximately 75 nm and they appeared to lie within the cisternae of granular endoplasmic reticulum. When cut longitudinally, the structures appeared as elongated tubes lying within the endoplasmic reticulum, but a number of ends were found where the inner membrane formed a closed tube and the outer membrane folded back and was continuous with the membrane forming the outer layer of the sac of endoplasmic reticulum. These profiles do not appear to have been described previously although similarities between their ultrastructure and that of the coat of certain unusual forms of Rhabdovirus are noted.

Alzheimer Disease↗
PubMed2004

Dynamic nucleation of Golgi apparatus assembly from the endoplasmic reticulum in interphase hela cells.

Models of Golgi apparatus biogenesis and maintenance are focused on two possibilities: one is self-assembly from the endoplasmic reticulum, and the other is nucleation by a stable template. Here, we asked in three different experimental situations whether assembly of the Golgi apparatus might be dynamically nucleated. During microtubule depolymerization, the integral membrane protein p27 and the peripheral Golgi protein GM130, appeared in newly formed, scattered Golgi elements before three different Golgi apparatus cisternal enzymes, whereas GRASP55, a medial peripheral Golgi protein, showed, if anything, a tendency to accumulate in scattered Golgi elements later than a cisternal enzyme. During Golgi formation after brefeldin A washout, endoplasmic reticulum exit of Golgi resident enzymes could be completely separated from that of p27 and GM130. p27 and GM130 accumulation was onto newly organized perinuclear structures, not brefeldin A remnants, and preceded that of a cisternal enzyme. Reassembly was completely sensitive to guanosine 5'-diphosphate-restricted Sar1p. When cells were microinjected with Sar1pWT DNA to reverse a guanosine 5'-diphosphate-restricted Sar1p endoplasmic reticulum-exit block phenotype, GM130 and p27 collected perinuclearly with little to no exit of a cisternal enzyme from the endoplasmic reticulum. The overall data strongly indicate that the assembly of the Golgi apparatus can be nucleated dynamically by GM130/p27 associated structures. We define dynamic nucleation as the first step in a staged organelle assembly process in which new component association forms a microscopically visible structure onto which other components add later, e.g. Golgi cisternae.

Antineoplastic Agents↗
PubMed1976

Protein phosphorylation of the smooth and rough endoplasmic reticulum in normal and neoplastic liver of the rat.

Smooth and rough endoplasmic reticulum from rat liver and hepatomas exhibited endogenous protein kinase activity independent of adenosine 3':5'-monophosphate. The phosphorylation of smooth membranes by this process was consistently higher than that of rough membranes. When histone was added along with the smooth endoplasmic reticulum, cyclic AMP stimulated protein phosphorylation. Analysis of membrane-phosphorylated proteins by gel electrophoresis showed 5 major phosphorylated bands with estimated molecular weights of 155 000, 62 000, 50 000, 46 000 and 43 000, whereas major bands having estimated molecular weights of 62 000, 50 000 and 43 000 were found in membranes of the smooth endoplasmic reticulum of the Morris hepatoma 5123 C. Since previous studies in this and other laboratories have demonstrated the similarity of the protein components of membranes of the endoplasmic reticulum of normal liver and hepatoma, our findings indicate an inability of the protein kinase of hepatoma intracellular membranes to phosphorylate protein species that are found in membranes of both liver and the neoplasm.

Animals↗
PubMed1979

The role of components of the endoplasmic reticulum in the biosynthesis of cytochrome P-450.

1. Antibodies have been prepared to rat hepatic cytochrome P-450 and their specificity demonstrated. These antibodies have been used to investigate the biosynthesis of cytochrome P-450 in vitro and in situ in various components of the endoplasmic reticulum. 2. A preparation of heavy rough endoplasmic reticulum translocates proteins newly biosynthesized in vitro vectorially into the luminal space and these are released by low concentrations of deoxycholate. A significant proportion of the radioactivity found in this released fraction is incorporated into cytochrome P-450. 3. Following incorporation of [14C]leucine by perfused rat liver, radioactively labelled cytochrome P-450 can be found in the intrascisternal content of heavy rough, light rough and smooth endopalsmic reticulum and also in a solublized Golgi preparation. 4. We suggest that at least part of the newly biosynthesized cytochrome P-450 is translocated into the intracisternal space of the rough endoplasmic and then passes through the other components of the endoplasmic reticulum before insertion at its ultimate membrane locus.

Animals↗
PubMed1980

A comparison of vesicles derived from terminal cisternae and longitudinal tubules of sarcoplasmic reticulum isolated from rabbit skeletal muscle.

Sarcoplasmic reticulum vesicles were separated into heavy (derived from terminal cisternae) and light (derived from longitudinal tubules) fractions, according to Meissner [Biochim. Biophys. Acta, 389, 51-68 (1975)]. The similar Ca2+ sensitivities of phosphoprotein formation, ATPase activity and calcium uptake, and the similar phosphoprotein turnover rates (ATPase/phosphoprotein formation) of both fractions indicate that the same ATPase enzyme is present in the terminal cisternae and longitudinal sarcoplaxmic reticulum. The higher V for Ca2+-activated ATPase activity and calcium uptake in the light fraction correlated with the higher concentration of ATPase enzyme per mg of membrane protein in this fraction. In both the presence and absence of calcium-precipitating anions, the light fraction stored more calcium than the heavy. The Ca2+ dependence of calcium release after addition of EGTA appeared similar in both fractions, but the rate of calcium release was more rapid in the light fraction. These findings suggest that calcium release may occur more rapidly from longitudinal than terminal cisternae portions of the sarcoplasmic reticulum and that calcium release, like calcium uptake, may be mediated by the ATPase enzyme in the sarcoplasmic reticulum membrane. Although the activation energies for Ca2+-activated ATPase activity above and below the transition temperature were significantly different for the heavy and light fractions, their transition temperatures were similar. Partial purification of the ATpase enzyme by deoxycholate treatment modified the activation energies of the light but not the heavy fraction and caused the activation energies to become similar. The phosphoprotein levels of heavy and light vesicles did not become similar after deoxycholate treatment, although gel electrophoretograms indicated both samples contained > 90% ATPase protein. These results indicate the protein-lipid associations in these two fractions may be different.

Adenosine Triphosphatases↗
PubMed1994

Thermal uncoupling of the Ca(2+)-transporting ATPase in sarcoplasmic reticulum. Changes in surface properties of light vesicles.

It is known that the light fraction of rabbit skeletal muscle sarcoplasmic reticulum vesicles can release Ca2+ from the intravesicular space, although the Ca(2+)-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 degrees C which quickly decreases the efficiency of Ca(2+)-transporting ATPase operation without any visible effects on the hydrolytic activity of the Ca(2+)-ATPase in the membranes. The treatment of the vesicles decreased the negative membrane surface potential created by the Ca(2+)-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 Ca(2+)-ATPase protein arrangement in the membrane indicated that the heat treatment induced protein oligomerization and some of the Ca(2+)-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 Ca(2+)-ATPase molecules. This protein rearrangement may create channels for calcium leakage from light sarcoplasmic reticulum vesicles.

Animals↗
PubMed1983

Ethanol-induced changes of granular endoplasmic reticulum in hepatocytes of mini-pig foetuses.

The present study describes the occurrence of oblong or oval membranous aggregations of the endoplasmic reticulum in the cytoplasm of hepatocytes from half-term mini-pig foetuses, whose mothers in addition to their ordinary sufficient fodder have been given ethanol in amounts comparable to those consumed by human alcoholics. The structure of the aggregations and their relation to the granular endoplasmic reticulum indicate that they represent a change of the granular endoplasmic reticulum, induced by ethanol. The oval aggregations show resemblances to concentric lamellar bodies described in hepatocytes altered by disease or by experimental procedures not involving ethanol. It is concluded that the change of granular endoplasmic reticulum is probably a sign of an injurious effect of ethanol on the foetal hepatocyte.

Animals↗
PubMed1998

cAMP-mediated signal transduction and sarcoplasmic reticulum function in heart failure.

There is evidence that the effects of beta-adrenergic receptor agonists on myocardial contractility result principally from the phosphorylation of phospholamban by cAMP-dependent protein kinase and the consequent deinhibition of SERCA2 activity and stimulation of sarcoplasmic reticulum Ca2+ transport. An impairment in beta-adrenergic receptor-stimulated cAMP generation, attributable to down-regulation of beta 1-adrenergic receptors and increased activity of G alpha i and G protein-coupled receptor kinase, has long been recognized in failing human myocardium. This impairment is associated with a compartment-specific decrease in sarcoplasmic reticulum cAMP content that may selectively reduce phospholamban phosphorylation. Published and preliminary results indicate that two plausible explanations for this compartment-specific decrease--a reduction in sarcoplasmic reticulum-associated cAMP-dependent protein kinase or an increase in sarcoplasmic reticulum-associated cAMP phosphodiesterase--are unlikely. Instead, there is reason to believe that the selective reduction in beta 1-adrenergic receptor density in failing myocardium is causally related to this compartment-specific decrease in cAMP content through an as-yet-undetermined mechanism. The fact that the modulation of SERCA2 activity by phospholamban is preserved in failing human myocardium offers an opportunity for improvement in the therapy of heart failure.

Adrenergic beta-Agonists↗
PubMed1989

Identification of the 16 degrees C compartment of the endoplasmic reticulum in rat liver and cultured hamster kidney cells.

In many systems transfer between the endoplasmic reticulum and the Golgi apparatus is blocked at temperatures below 16 degrees C. In virus-infected cells in culture, a special membrane compartment is seen to accumulate. Our studies with rat liver show a similar response to temperature both in situ with slices and in vitro with isolated transitional endoplasmic reticulum fractions. With isolated transitional endoplasmic reticulum fractions, when incubated in the presence of nucleoside triphosphate and a cytosol fraction, temperature dependent formation of vesicles occurred with a Q10 of approximately 2 but was apparent only at temperatures greater than 12 degrees C. A similar response was seen in situ at 12 degrees C and 16 degrees C where fusion of transition vesicles with cis Golgi apparatus, but not their formation, was blocked and transition vesicles accumulated in large numbers. At 18 degrees C and below and especially at 8 degrees C and 12 degrees C, the cells responded by accumulating smooth tubular transitional membranes near the cis Golgi apparatus face. With cells and tissue slices at 20 degrees C neither transition vesicles nor the smooth tubular elements accumulated. Those transition vesicles which formed at 37 degrees C were of a greater diameter than those formed at 4 degrees C both in situ and in vitro. The findings show parallel responses between the temperature dependency of transition vesicle formation in vitro and in situ and suggest that a subpopulation of the transitional endoplasmic reticulum may be morphologically and functionally homologous to the 16 degrees C compartment observed in virally-infected cell lines grown at low temperatures.

Adenosine Triphosphate↗