Spatial fluctuations of loose spin coupling in CuMn/Co multilayers.

A detailed investigation of magnetic impurity-mediated interlayer exchange coupling observed in Cu(0.94)Mn(0.06)/Co multilayers using polarized neutron reflectometry and magnetic x-ray techniques is reported. Excellent descriptions of temperature and magnetic field dependent biquadratic coupling are obtained using a variant of the loose spin model that takes into account the distribution of the impurity Mn ions in three dimensions. Positional disorder of the magnetic impurities is shown to enhance biquadratic coupling via a new contribution J(2)(fluct), leading to a temperature dependent canting of magnetic domains in the multilayer. These results provide measurable effects on RKKY coupling associated with the distribution of impurities within planes parallel to the interfaces.

Intracellular axial current in Chara corallina reflects the altered kinetics of ions in cytoplasm under the influence of light.

Recent experiments demonstrate that the concentration of Ca2+ in cytoplasm of Chara corallina internodal cells plays important role in electrical excitation of the plasma membrane. The concentration of free Ca2+ in the cytoplasm -[Ca2+]c is also sensitive to visible light. Both phenomena were simultaneously studied by noninvasive measuring action potential (AP) and magnetic field with a superconducting quantum interference device magnetometer in very close vicinity of electrically excited internodal C. corallina cells. A temporal shift in the depolarization maximum, which progressively occurred after transferring cells from the dark into the light, can be explained by the extended Othmer model. Assuming that the change in membrane voltage during the depolarization part of AP is the direct consequence of an activation of [Ca2+]c sensitive Cl- channels, the model simulations compare well with the experimental data. We can say that we have an example of electrically elicited AP that is of biochemical nature. Electric and magnetic measurements are in good agreement.

Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites.

CCl4-induced liver damage was modeled in monolayer cultures of rat primary hepatocytes with a focus on involvement of covalent binding of CCl4 metabolites to cell components and/or peroxidative damage as the cause of injury. (1) Covalent binding of 14C-labeled metabolites was detected in hepatocytes immediately after exposure to CCl4. (2) Low oxygen partial pressure increased the reductive metabolism of CCl4 and thus covalent binding. (3) [14C]-CCl4 was bound to lipids and to proteins throughout subcellular fractions. Binding occurred preferentially to triacylglycerols and phospholipids, with phosphatidylcholine containing the highest amount of label. (4) The lipid peroxidation potency of CCl4 revealed subtle differences compared to other peroxidative substances, viz., ADP-Fe3+ and cumol hydroperoxide, respectively. (5) CCl4, but not the other peroxidative substances, decreased the rate of triacylglycerol secretion as very low density lipoproteins. (6) The anti-oxidant vitamin E (alpha-tocopherol) blocked lipid peroxidation, but not covalent binding, and secretion of lipoproteins remained inhibited. (7) The radical scavenger piperonyl butoxide prevented CCl4-induced lipid peroxidation as well as covalent binding of CCl4 metabolites to cell components, and also restored lipoprotein metabolism. The results confirm that covalent binding of the CCl3* radical to cell components initiates the inhibition of lipoprotein secretion and thus steatosis, whereas reaction with oxygen, to form CCl3-OO*, initiates lipid peroxidation. The two processes are independent of each other, and the extent to which either process occurs depends on partial oxygen pressure. The former process may result in adduct formation and, ultimately, cancer initiation, whereas the latter results in loss of calcium homeostasis and, ultimately, apoptosis and cell death.

Hepatocyte damage induced by carbon tetrachloride: inhibited lipoprotein secretion and changed lipoprotein composition.

Changes of lipoprotein secretion and composition in response to CCl4 treatment were studied in monolayer cultures of rat primary hepatocytes. (1) CCl4 decreased secretion of very low density lipoproteins (VLDL) by about 85%, while high density lipoprotein (HDL) secretion was less affected (about 40%). The effect was concentration-dependent. (2) CCl4 significantly inhibited secretion of VLDL- and HDL-associated triglycerides and cholesterol esters. VLDL- and HDL-associated cholesterol was not affected, while secretion of phospholipids was increased. (3) Hepatocytes secreted the apolipoproteins B48, B100, E, C, and A-I. CCl4 reduced secretion of apoproteins associated with VLDL by almost 20%, and by about 75% when associated with HDL. The de novo synthesis of apolipoproteins was attenuated by CCl4. (4) CCl4 caused variations in the apolipoprotein composition in VLDL and HDL. CCl4 intoxication of the liver affected the morphology and/or function of the lipoproteins, which drastically impaired their ability to act as transport vehicles for lipids from the liver to the circulation.

Early functional apoptotic responses of thymocytes induced by Tri-n-butyltin.

BACKGROUND: Programmed cell death, also termed apoptosis, is the main focus of interest in a variety of scientific and clinical areas. For a better understanding of the mechanisms of apoptosis, from the onset of the cellular death program to the late stages of apoptosis or apoptotic necrosis, very early functional events have to be quantified because they might be involved in temporal and causal relationships between apoptosis-related key processes. METHODS: We have established a flow cytometric technique to quantify time-dependent signals simultaneously with high temporal resolution (Deltat = 1 s) in living cells. With this technique, the response of cells to apoptosis-stimulating agents can be analyzed over 15 min. For this purpose, a thermostatted sample tube holder for repeatable interruption-free injection of substances into the cell suspension was developed. Early detectable fluorescence and scatter parameters were related to intracellular free Ca2+ concentration, [Ca2+]i (Indo-1 fluorometry), membrane permeability (propidium iodide [PI] influx), and cell volume (forward scatter). RESULTS: A T-cell line (Jurkat) served as a model system. Apoptosis was induced by the biozid Tri-n-butyltin (TBT). Dependent on the TBT concentration (0.3-10 microM), the mean free [Ca2+]i increased by a factor of 1.2-6 during a short time interval of just 2 min. Especially after low TBT concentrations (< 0.5 microM), this [Ca2+]i increase was nearly transient during the observation time of 15 min. Higher TBT concentrations (0.5-10 microM), however, induced a transient increase of [Ca2+]i (Ca-TR) only in a fraction of the cells; in another subpopulation, a steady-state Ca2+ signal (Ca-SST) was observed. The analysis of the simultaneously registered PI signals of the Ca-SST cells showed a shift to increasing PI fluorescence (by a factor of about 4) with increasing Ca2+ concentrations. In Ca-TR cells, the PI fluorescence remained nearly unchanged. These apoptosis-related changes (increase in [Ca(2+)]i and membrane permeability) could be confirmed by the additional observation of a TBT concentration-dependent decrease in cell volume measured during the same early time period. CONCLUSIONS: The simultaneously analyzed parameters (i.e., [Ca2+]i, membrane permeability, and cell volume) suggested that, in our model system of Jurkat T-cells treated with TBT, an apoptotic cell fate was indicated very early (within 15 min) by the steady-state [Ca2+]i level.

Pathogenesis of carbon tetrachloride-induced hepatocyte injury bioactivation of CCI4 by cytochrome P450 and effects on lipid homeostasis.

The CCl4-induced development of liver damage was studied in monolayer cultures of primary rat hepatocytes: (1) CCl4 caused accumulation of triglycerides in hepatocytes following cytochrome P450 induction with beta-naphthoflavone or metyrapone. Ethanol or a high dose of insulin plus triiodothyronine had the same effect. (2) CCl4 increased the synthesis of fatty acids and triglycerides and the rate of lipid esterification. Cholesterol and phospholipid synthesis from acetate was also increased. (3) CCl4 reduced beta-oxidation of fatty acids as assessed by CO2-release and ketone body formation. Hydrolysis of triglycerides was also reduced. (4) The content of unsaturated fatty acids in microsomal lipids was decreased by almost 50% after incubation with CCl4, while saturated fatty acids increased slightly. (5) CCl4 exerted a pronounced inhibitory effect on the exocytosis of macromolecules (albumin), but did not affect secretion of bile acids from hepatocytes.

Simultaneous recording of calcium transients and reactive oxygen intermediates of human polymorphonuclear granulocytes in response to formyl-Met-Leu-Phe and the environmental agent sulfite.

BACKGROUND: Human polymorphonuclear granulocytes (PMN) are an essential component in the immunological defense network against a variety of harmful pathogens. We have studied the effects of the airborne pollutant sulfite on the calcium metabolism and respiratory burst of these cells simultaneously. METHODS: A flow cytometric method was developed using the fluochromes Indo-1 and DHR-123. This method allowed us to investigate the real-time kinetics of intracellular free calcium and reactive oxygen intermediates in viable cells with a temporal resolution of 1 s over a time course of 17 min. An additional feature was the possibility to discriminate between reacting and nonreacting cells after treatment with defined stimuli, thus gaining additional insight into the behavior of cell subpopulations. RESULTS: We analyzed the effects of sulfite on PMN before and after stimulation with formyl-Met-Leu-Phe (FMLP). Treatment with sulfite alone (0.001-1 mM) caused a small, nontransient increase in intracellular calcium. Preincubation with sulfite reduced the maximal calcium response elicited by FMLP. A significant increase in steady-state calcium levels after stimulation with FMLP was observed after treatment with sulfite in concentrations of 10 and 100 mM. Regarding the respiratory burst, treatment with sulfite alone in concentrations of 0.001-1 mM induced a significant increase in DHR-123-derived fluorescence, whereas concentrations of 5 and 10 mM caused a significant depression of this fluorescence below baseline values. Sulfite caused a maximal twofold increase of DHR-123-derived fluorescence compared with the FMLP response. Similar results were obtained after preincubation with sulfite before treatment with FMLP, showing that the effect of sulfite on the respiratory burst was additive to the FMLP response. Regarding the fractions of responding cells, treatment with sulfite up to 1 mM induced a concentration-dependent increase of burst-reactive PMN, whereas preincubation before stimulation with FMLP showed no correlation between sulfite concentration and fraction of burst-reacting cells. CONCLUSIONS: By simultaneous registration of [Ca(2+)](i) and [H(2)O(2)](i) of PMN after treatment with FMLP and sulfite, the essential responses were already observed within a short time interval (15 min). Striking differences were found in the response of calcium as second messenger and respiratory burst in PMN treated with sulfite. Until a critical concentration (0. 5-1 mM), sulfite caused a concentration-dependent increase of [H(2)O(2)](i), in addition to the FMLP-induced response. The [Ca(2+)](i) changes induced by sulfite alone, however, were found to be small and showed no correlation with the respiratory burst response.

In vivo and in vitro studies on the regulatory link between 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase in rat liver.

The activities of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoA reductase; EC 1.1.1.34), rate-limiting enzyme of cholesterol biosynthesis, and cholesterol 7 alpha-hydroxylase (EC 1.14.13.17), key enzyme of the neutral bile acid synthesis pathway, were measured in the microsomal fraction of rat liver and in rat liver cells to investigate the coordinate regulation of the two pathways. Both enzyme activities exhibited the same diurnal rhythm and responded in a coordinate fashion to fasting or bile acid-feeding (decrease) and to cholestyramine-feeding (increase). Cholesterol-feeding decreased the activity of HMGCoA reductase, increased that of cholesterol 7 alpha-hydroxylase, and concomitantly increased free cholesterol in microsomes. In an ex vivo setting using primary hepatocytes from animals fed a high cholesterol diet the activity of HMGCoA reductase was initially low and that of cholesterol 7 alpha-hydroxylase was elevated. Release of cholesterol into the medium with ongoing incubation caused HMGCoA reductase activity to increase, and that of cholesterol 7 alpha-hydroxylase to decline. Incubation of hepatocytes with a cholesterol-containing lipoprotein fraction stimulated the activity of cholesterol 7 alpha-hydroxylase, but left HMGCoA reductase activity unaffected. The results confirm the idea of a joint regulation of the two key enzymes of cholesterol metabolism in response to the levels of substrate and metabolites, and support the notion that with respect to bile acid and cholesterol levels, respectively, regulation of HMGCoA reductase activity may be secondary to that of cholesterol 7 alpha-hydroxylase. The in vitro studies supply evidence that the effects of cholesterol and bile acid excess or deficiency are direct and do not involve accessory changes of hormone levels or mediators.

The enzyme inducers 3-methylcholanthrene and phenobarbital affect the activities of glucocorticoid hormone-regulated enzymes in rat liver and kidney.

3-Methylcholanthrene, an inducer of P448-type cytochromes (mostly 1A1 and 1A2), and phenobarbital, an inducer of P450-type cytochromes (mostly 2B1 and 2B2), are prototypical for the actions of many xenobiotics. They cause endocrine disruption by affecting, among others, steroid hormone levels. Rats were treated with single bolus doses of 3-methylcholanthrene or phenobarbital, and enzyme activities that are controlled by glucocorticoids were measured in liver and kidney. The activities of the cytosolic enzymes L-alanine aminotransferase, indoleamine 2,3-dioxygenase (L-tryptophan pyrrolase), phosphoenolpyruvate carboxykinase, L-serine dehydratase and L-tyrosine aminotransferase were affected in a similar fashion: an initial activity reduction followed by two overshoots of activity 1 and 2 days after dosing. 3-Hydroxy-3-methylglutaryl coenzyme A reductase, the microsomal key enzyme of sterol synthesis, responded with a temporary reduction of activity only and evidently lost its diurnal rhythm. The time course of these changes is most likely caused by a combination of sub-physiological levels of glucocorticoids plus changes of other regulatory hormones elicited by feed intake, postprandial state, etc. A possible role for a combined action of the arylhydrocarbon (Ah) and glucocorticoid receptors in the effects of 3-methylcholanthrene is also suggested.

Polychlorinated biphenyls affect the activities of gluconeogenic and lipogenic enzymes in rat liver: is there an interference with regulatory hormone actions?

1. The effects of dietary polychlorinated biphenyls (PCBs) (30-2000 ppm) on activities of gluconeogenic (phosphoenolpyruvate carboxykinase-PEPCK, and fructose 1,6-bisphosphatase-FdPase) and lipogenic enzymes (fatty acid synthase-FAS, ATP citrate lyase-ACL, malic enzyme-ME, glucose 6-phosphate dehydrogenase-G6PDH, and 6-phosphogluconate dehydrogenase-PGDH) were studied in livers of the female Sprague-Dawley and Wistar rat. 2. PCB amounts accumulating in the liver reflected the extent of dietary exposure. The Wistar strain was more sensitive to PCBs than the Sprague-Dawley strain. Of the Clophentype PCBs those containing 60 and 64% chlorine displayed the most pronounced effects. 3. Activities of gluconeogenic enzymes (PEPCK and FdPase) were dose-dependently decreased by PCBs, PEPCK being considerably more sensitive. This decrease was also found under conditions where the activity of PEPCK was induced (administration of adrenalin, glucagon or cAMP, feeding high protein diets, starvation). 4. Activities of lipogenic enzymes were induced by PCBs. The increase was much greater with ME, G6PDH and PGDH (up to 10-fold) than with FAS and ACL (approximately 2-fold). PCB effects were dose-dependent, but transient. 5. In cultured hepatocytes basal activities of lipogenic enzymes were induced by PCBs in the absence of hormones. With saturating levels of insulin or triiodothyronine, enzyme activities were also induced, but addition of PCBs resulted in an additive effect. 6. These results suggest that in the female rat PCBs can mimic the actions of certain hormones by affecting either hormone levels, hormone receptor systems or regulatory systems.

Binding of Cu to metallothionein in tissues of the LEC rat with inherited abnormal copper accumulation.

Long-Evans Cinnamon (LEC) rats aged 16 +/- 4 weeks with histopathological alterations of liver and kidney, exhibited elevated Cu levels in liver, kidney and spleen which were 52, 27 and 5 times higher than those of the respective tissues of age-matched Wistar rats. About 61% of hepatic and about 38% of renal Cu was recovered in the cytosolic fraction. Metallothionein (MT) levels were found to correlate with the cytosolic Cu concentrations in liver and kidney. According to differential MT analysis, about 68 and 82% of hepatic and renal MT was loaded with Cu. The portion of MT which binds Cu was negatively correlated with the ratio of cytosolic Zn/Cu in all organs investigated. Despite high MT levels and the high percentage of Cu binding to MT, particularly in liver and kidney, considerable amounts of Cu remained unbound to MT. This non-MT bound Cu showed good correlation with the total cytosolic Cu content, and might play a crucial role in the pathogenesis of Cu toxicosis.

Nutritional regulation of the activities of lipogenic enzymes of rat liver and brown adipose tissue.

Nutrition-induced effects on the activity of enzymes of lipogenesis, fatty acid synthase (FAS: EC 2.3.1.85), ATP citrate lyase (ACL: EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH: EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and interscapular brown adipose tissue (BAT) of rats. The lipogenic enzymes could be grouped into two categories according to their response to dietary manipulations: FAS and ACL, both key enzymes of lipogenesis, responded fast and strongly to dietary manipulations. ME, G6PDH and PGDH, enzymes which also contribute to metabolic pathways other than lipogenesis, responded in a more sustained and less pronounced fashion. Feed deprivation caused the specific activities of lipogenic enzymes to decline several-fold. Refeeding of previously fasted (up to 3 days) animals increased the activities dramatically (10-to 25-fold) to far above pre-fasting levels ("overshoot"). Repetition of the fasting/refeeding regimen increasingly impaired the ability of both tissues to synthesize overshooting enzyme activities in the subsequent refeeding period. The fasting-induced decline of the activities was prevented when sugars were provided to the animals via drinking water. The sugars displayed different effectivities: sucrose = glucose > fructose > maltose > > lactose. Sugars as the sole nutrient after fasting were also able to induce overshooting enzyme activities. Again, activities of FAS and ACL responded in a more pronounced fashion than the other three enzymes. Transition from feeding one diet to feeding a new diet of different composition led to adaptation of the lipogenic enzyme activities to levels characteristic for the new diet. Replacing a low-carbohydrate with a high-carbohydrate diet proceeded with major alterations of enzyme activities. This process of attaining a new level took up to 20 days and involved pronounced oscillations of the specific activities. In contrast, when a high-carbohydrate diet was replaced with another diet. particular one high in fat, transition to new enzyme activities was completed within 2-3 days and proceeded without oscillations. All dietary manipulations caused more pronounced responses in young (35d-old) than in adult (180d-old) animals.

Suppression of agonist induced Ca2+ oscillations in cultured hepatocytes by nafenopin: possible involvement of protein kinase C.

The alpha 1-agonist phenylephrine (5 microM) induces an increase in the free cytosolic Ca2+ concentration, followed by repetitive transients of the cytoplasmic Ca2+ concentration, in single Fura-2 loaded hepatocytes. The tumor promoting, hypolipidemic drug nafenopin suppressed the cellular Ca2+ response to phenylephrine. The effect of nafenopin on the Ca2+ increase and Ca2+ oscillations was largely prevented by the specific protein kinase C inhibitor Gö 6976. This finding suggests involvement of protein kinase C in the action of nafenopin on phenylephrine induced Ca2+ mobilization.

The response of rat serum lipids to diets of varying composition or contaminated with organochlorine pesticides.

The effects of different diets (high carbohydrate, high protein, high fat) and diets contaminated with polychlorinated biphenyls (PCBs) and/or gamma-hexachlorocyclohexane (lindane) on the levels of serum triglycerides, cholesterol and phospholipids were investigated in Wistar rats. Serum triglyceride levels differed significantly among the diets, while those of cholesterol and phospholipids were much less affected by the diet composition. A change in diet composition resulted in a gradual adaptation to the lipid levels characteristic of the new diet with major variations including oscillations. There was, however, no specific component of a diet that could be associated with any specific change in serum lipids. While feed deprivation decreased the serum lipids (40-65% in 3 days), refeeding the starved animals caused pronounced increases of the lipids that were different among the diets. The response of the triglyceride levels was the strongest (up to 10 times the starvation levels) followed by those of the phospholipids (4-fold) and cholesterol (2.5-fold). Response of the triglyceride levels peaked within 1 or 2 days of refeeding, whereas those of cholesterol and phospholipids took 4 days to reach the maximum. Feeding PCB-contaminated diets increased the serum lipids in a dose-dependent manner (15-250 ppm). Higher PCB concentrations were increasingly inhibitory (350 ppm) or overtly toxic (> 400 ppm). Elevated lipids returned to the starting levels immediately after peaking (triglycerides) or only after several days (cholesterol, phospholipids) but with an earlier onset at lower PCB concentrations. Refeeding starved animals with PCB-contaminated diets also increased the serum lipids dose-dependently. Feeding lindane-containing diets (50-150 ppm) as well as refeeding animals with lindane diets resulted in a considerable increase of the triglyceride levels, while cholesterol and phospholipids increased much less. Higher lindane concentrations (250 ppm) were inhibitory. The outcome on serum lipid levels on feeding diets contaminated with both PCBs and lindane was basically additive.

The effect of gamma-hexachlorocyclohexane (lindane) on the activities of liver lipogenic enzymes and on serum lipids in rats.

The effect of dietary gamma-hexachlorocyclohexane (lindane) (50-350 ppm, 0.17-1.19 mumol/kg chow) on the activity of enzymes of lipogenesis, viz., fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44), and on serum lipid levels, was investigated in livers of 35-day-old male Wistar rats. Lindane (150 ppm) caused a substantial decline of enzyme activities within the first 24 h of treatment. The decrease was transient, however, and enzyme activities subsequently recovered despite continuation of lindane feeding. The recovery of enzyme activities was comparatively fast in the case of ME, G6PDH and PGDH, but very slow with FAS and CCE. Activities of lipogenic enzymes decrease when animals are starved, and increase much beyond prestarvation levels upon subsequent refeeding. Lindane in the refeeding diet blunted this overshoot of FAS and CCE activities in a dose-dependent manner. In contrast, activities of Me, G6PDH and PGDH responded to low dietary lindane concentrations with a substantial stimulation of the increase of activity, whereas at high lindane concentrations the overshoot was inhibited. According to their responses to lindane exposure, liver lipogenic enzymes could be grouped into 2 categories with FAS and CCE representing one and ME, G6PDH and PGDH representing the other group. Polychlorinated biphenyls (PCBs) in the diet caused basically opposite changes of the activities of the lipogenic enzymes. Co-administration of lindane and PCBs resulted in an apparent cancellation of effects, suggesting that lindane and PCBs affect fatty acid synthesis at opposite points.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipogenic enzymes of rat liver and adipose tissue. Dietary variations and effect of polychlorinated biphenyls.

The lipogenic enzymes fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and in brown adipose tissue (BAT) of Wistar rats under various dietary conditions and in the presence of 15 to 250 ppm (approximately 0.045-0.75 mumol/kg chow) polychlorinated biphenyls (PCBs). In response to refeeding starved animals, enzyme activities in both tissues increased to above normal levels and thereafter exhibited pronounced oscillations of their activities. The extent of increase depended on the carbohydrate and fat content of the diet. The lipogenic enzymes could be grouped in two categories according to their sensitivity to dietary carbohydrate: FAS and CCE responded faster to smaller changes in dietary composition, while ME, G6PDH and PGDH required larger changes and more time to respond. Diet-induced alterations of enzyme activities were of the same order of magnitude in liver and BAT. They were age-dependent, being more pronounced in young animals. Independent of the type of dietary manipulations, activities changed in a coordinate fashion, i.e., the changes of the activities of all 5 enzymes occurred at similar ratios to each other with an identical time course. Feeding PCB-containing diets resulted in a considerable increase of the activities of the lipogenic enzymes in liver, which was significantly greater with ME, G6PDH and PGDH. The effect was dose-dependent but transient. In liver the response to PCB feeding was identical in male and female animals, whereas in BAT lipogenic activities increased in females, but decreased in males. Refeeding starved animals with a PCB-containing diet led to an additional stimulation of the normal refeeding-induced increase of the enzyme activities in liver and BAT. This PCB-induced increase was 2-fold for FAS and CCE, but up to 15-fold for the other enzymes. All PCB-induced effects were significantly less pronounced in old than in young animals. In primary hepatocytes activities increased in hormone-free medium in the presence of PCBs. While activity was induced in insuline- and triiodothyronine-containing medium, this increase was significantly greater with PCBs present.

Magnesium-dependent calcium efflux in mammalian heart muscle.

Extra and intracellular magnesium is involved in the control of myocardial calcium movements. Here we report on an increase in cytosolic calcium concentration in resting ventricular myocytes due to the withdrawal of extracellular magnesium under the condition of a blocked sodium-dependent calcium elimination. Evidence for an activation of cellular calcium efflux by extracellular magnesium showed experiments in perfused hearts. It is concluded that extracellular magnesium can modulate the intracellular free calcium concentration of the myocardial cells by its influence on calcium elimination.