Angiostrongylus cantonensis: Biogenic amines in the lungs of infected rats

Levels of histamine, serotonin, norepinephrine, and dopamine were estimated sequentially in rats parasitized by the lungworm, Angiostrongylus cantonensis, between 30 and 75 days postinfection. The highest level of histamine in the infected lungs was 52.19 μg/g wet wt tissue, 13 times higher than the level found in control rats. The level of serotonin rose from the normal level of 6.41 to 10.27 μg/g wet wt tissue after the worms had lodged in the pulmonary artery for 15 days. There were no changes in norephinephrine or dopamine. Studies of host cell response to infection revealed that the increased histamine and serotonin levels corresponded to a rise in the lung population of mast cells, suggesting that these cells produced the amines.     

Mast cells of the lungs in experimental hyperergic pleurisy

Reaction of mast cells, the content of free and cell histamine and serotonin in the lung tissue at early stage of inflammation were studied on the model of hyperergic pleurisy in albino rats. Intrapleural antigen injection to sensitized rats was followed by progressive degranulation of mast cells of pleural and subpleural lung tissue with release of histamine and serotonin. The maximal increase in the content of free amines was found after 15 min. The level of free amines did not differ significantly from the initial one by the first hour. The early activation of amines synthesis and their storage recovery were observed as well as reactions of the late phase of immunological activation in the mast cells as a leukocytic tissue infiltration by subsequently polymorphonuclear leukocytes and macrophages.     

Gender differences in the histamine and serotonin content of blood,peritoneal and thymic cells: a comparison with mast cells

The serotonin and histamine content of mast cells and white blood cells in adult male and female rats was compared, using a flow cytometric immunological method. Serotonin was significantly higher in female peritoneal mast cells, peritoneal monocyte-ganulocyte-macrophage cells, blood lymphocytes and blood thymocytes. Histamine was significantly higher in female peritoneal monocyte-granulocyte-macrophage cells, and blood lymphocytes, monocytes and granulocytes, but was significantly less in thymocytes. Peritoneal lymphocytes and the monocyte-granulocyte-macrophage group contained significantly more histamine than mast cells. These experiments call attention to gender differences in the levels of biogenic amines in cells participating in defence reactions, and to the possible non-unique role of mast cells in serotonin and histamine supply.     

Amines of the mucosal mast cell of the gut in normal and nematode infected rats

Infection with the nematode N. brasiliensis is accompanied by a marked increase of the number of mucosal mast cells (MMC) and the mucosal content of histamine and 5-hydroxytryptamine (5-HT). We compared amine levels, determined by ion exchange and high performance liquid chromatography (HPLC) with numbers of MMC and enterochromaffin cells (ECC). Furthermore, we measured 5-HT cytofluorometrically in individual MMC and ECC. The cellular distribution of 5-HT was studied immunohistochemically. Our results corroborate previous findings that histamine is stored in MMC. Quotients between histamine content and numbers of MMC decreased throughout the period of worm expulsion, followed by a recovery, suggesting a histamine release during this defense reaction. The HPLC analysis gave no evidence for a storage of dopamine in MMC. ECC and MMC of normal and infected rats showed a formaldehyde induced fluorescence and 5-HT immunoreactivity. The formaldehyde induced fluorescence of MMC from normal rats was about 10% that of ECC, but MMC exceeded ECC three times by numbers. These findings suggest that a considerable proportion of the intestinal 5-HT in the normal rat is stored in MMC. ECC numbers did not change during the infection and their content of 5-HT was unchanged, as judged by cytofluorometry. The cytofluorometric measurements showed that the intensity of the monoamine fluorescence from the MMC of infected animals was about three times as high as that of controls. It was concluded that the increased tissue levels of 5-HT was due to both an increase in MMC numbers and an increase in the 5-HT content of individual MMC. The results suggest a different role for histamine and 5-HT in the defense reaction towards the nematode infection.     

Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to maintain thermogenesis

Lysosomal acid lipase (LAL) is the only known enzyme, which hydrolyzes cholesteryl esters and triacylglycerols in lysosomes of multiple cells and tissues. Here, we explored the role of LAL in brown adipose tissue (BAT). LAL-deficient (Lal?/?) mice exhibit markedly reduced UCP1 expression in BAT, modified BAT morphology with accumulation of lysosomes, and mitochondrial dysfunction, consequently leading to regular hypothermic events in mice kept at room temperature. Cold exposure resulted in reduced lipid uptake into BAT, thereby aggravating dyslipidemia and causing life threatening hypothermia in Lal?/? mice. Linking LAL as a potential regulator of lipoprotein lipase activity, we found Angptl4 mRNA expression upregulated in BAT. Our data demonstrate that LAL is critical for shuttling fatty acids derived from circulating lipoproteins to BAT during cold exposure. We conclude that inhibited lysosomal lipid hydrolysis in BAT leads to impaired thermogenesis in Lal?/? mice.     

Protein phosphorylation during mast cell secretion in radioprophylaxis

A study was made of the role of protein phosphorylation of mast cells and their cytoskeleton upon secretion induced by biogenic amines (histamine and serotonin) and bradykinin, a possible mediator of the effect of MEA, a sulfur-containing radioprotector. The data obtained indicate that the incorporation of phosphate in some proteins of mast cells is an important stage in the process of exocytosis during radioprophylaxis. Cytoskeletal proteins were shown to be involved in mast cell secretion.     

寒冷诱导产热时大鼠棕色脂肪能量代谢相关蛋白谱的变化

棕色脂肪组织(BAT)的生理作用与白色脂肪显著不同,它以产热的形式释放能量而不是将能量以ATP的形式储存．线粒体是在能量代谢和维持细胞稳态中具有重要功能的细胞器．为了更好地了解棕色脂肪中的能量代谢过程,运用双向电泳及质谱相结合的技术,分离了大鼠白色和棕色脂肪线粒体,对其差异蛋白质谱进行了系统分析和鉴定．参与脂肪和氨基酸代谢、三羧酸循环及线粒体呼吸链的蛋白质在棕色脂肪线粒体中的表达明显高于白色脂肪线粒体,在寒冷诱导下这些蛋白质的表达进一步上调．此外,参与辅酶Q合成的一系列COQ 基因在棕色脂肪中经寒冷适应后表达明显上调．该研究表明,辅 酶Q合成的增高在非颤栗性产热中具有重要作用,为进一步了解棕色脂肪特异性的能量代谢提供了新的思路．     

Melatonin induces hypertrophy of brown adipose tissue in Spermophilus tridecemlineatus

Nonshivering thermogenesis (NST) plays an important role in hibernators during cold exposure and arousal periods. Brown adipose tissue (BAT), an important site of NST, displays seasonal changes in S. tridecemlineatus while cold exposure and short photoperiods stimulate hypertrophy of BAT.The pineal gland and melatonin have been implicated in thermoregulation but relatively little is known about the pineal's role in hibernation. In this investigation chronic melatonin administration via both silicone rubber implants containing 3 mg of melatonin and daily intraperitoneal injections of saline containing 50 μg of melatonin induced hypertrophy of BAT in young-of-the-year S. tridecemlineatus. Chronic melatonin administration appears to mimic the effects of cold exposure and/or short photoperiods on the hypertrophy of BAT.     

Uptake and turnover of dopamine in rat mast cells studied by cytofluorometry and high performance liquid chromatography

Summary Uptake and turnover of dopamine (DA) in rat peritoneal mast cells were studied by a cytofluorometric technique. The main advantage of the method is that it permits the study of the distribution of amine content within populations of cells. Catecholamines and indolamines can be differentiated, but subtler structural differences in this group of compounds cannot be distinguished. We, therefore, combined the cytofluorometric measurements with a liquid chromatographic method based on reversed-phase chromatography followed by amperometric detection in a thin layer flow cell. Intraperitoneally injectedl-DOPA was rapidly decarboxylated to DA, which was accumulated in mast cell granules. The elimination of DA from the mast cells was much faster than previously published 5-hydroxytryptamine and histamine elimination rates. No evidence of intracellular conversion of DA before its elimination was found and simultaneous heparin quantitations gave no evidence of an elimination pathway due to exocytosis of granules. Electron microscopy disclosed no structural changes that could be related to exocytosis during the elimination phase of DA. The rapid elimination together with absence of inhibition of DA-uptake after storage of exogenous 5-hydroxytryptamine suggest that the mechanism of DA storage differs from the mechanism of storage of endogenous mast cell amines.     

Prolonged effect of a single serotonin treatment in adult age on the serotonin and histamine content of white blood cells and mast cells of rats

Hormonal imprinting was provoked by serotonin treatment in adult age. Three weeks after treatment with 100 microg serotonin, the serotonin and histamine content of peritoneal cells (mast cells, lymphocytes and the monocyte-macrophage-granulocyte group), white blood cells (lymphocytes, granulocytes and monocytes) and thymic lymphocytes was studied by flow cytometry. The content of both amines was significantly higher in the mast cells of males and lower in females. Blood lymphocytes contained a higher serotonin and histamine level in males, and a lower serotonin level in females. The peritoneal monocyte-macrophage-granulocyte group contained less serotonin in both males and females. Thymocytes contained higher levels of both amines in females and higher histamine level in males. The experiments demonstrate that a single treatment at adult age can provoke imprinting, which alters-in the present case-the serotonin and histamine content of immune cells durably.     

Adaptive Activation of Thyroid Hormone and Energy Expenditure

The mechanisms by which thyroid hormone accelerates energy expenditure are poorly understood. In the brown adipose tissue (BAT), activation of thyroid hormone by type 2 iodothyronine deiodinase (D2) has been known to play a role in adaptive energy expenditure during cold exposure in human newborns and other small mammals. Although BAT is not present in significant amounts in normal adult humans, recent studies have found substantial amounts of D2 in skeletal muscle, a metabolically relevant tissue in humans. This article reviews current biological knowledge about D2 and adaptive T3 production and their roles in energy expenditure.     

Intermittent Cold Exposure Enhances Fat Accumulation in Mice

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis.     

The consequences of acute cold exposure on protein oxidation and proteasome activity in short-tailed field voles,microtus agrestis

During cold exposure, animals upregulate their metabolism and food intake, potentially exposing them to elevated reactive oxygen species (ROS) production and oxidative damage. We investigated whether acute cold (7 +/- 3 degrees C) exposure (1, 10, or 100 h duration) affected protein oxidation and proteasome activity, when compared to warm controls (22 +/- 3 degrees C), in a small mammal model, the short-tailed field vole Microtus agrestis. Protein carbonyls and the chymotrypsin-like proteasome activity were measured in plasma, heart, liver, kidney, small intestine (duodenum), skeletal muscle (gastrocnemius), and brown adipose tissue (BAT). Trypsin-like and peptidyl-glutamyl-like proteasome activities were determined in BAT, liver, and skeletal muscle. Resting metabolic rate increased significantly with duration of cold exposure. In skeletal muscle (SM) and liver, protein carbonyl levels also increased with duration of cold exposure, but this pattern was not repeated in BAT where protein carbonyls were not significantly elevated. Chymotrpsin-like proteasome activity did not differ significantly in any tissue. However, trypsin-like activity in SM and peptidyl-glutamyl-like activity in both skeletal muscle and liver, were reduced during the early phase of cold exposure (1-10 h), correlated with the increased carbonyl levels in these tissues. In contrast there was no reduction in proteasome activity in BAT during the early phase of cold exposure and peptidyl-glutamyl-like activity was significantly increased, correlated with the lack of accumulation of protein carbonyls in this tissue. The upregulation of proteasome activity in BAT may protect this tissue from accumulated oxidative damage to proteins. This protection may be a very important factor in sustaining uncoupled respiration, which underpins nonshivering thermogenesis at cold temperatures.     

Cold exposure increases glucose utilization and glucose transporter expression in brown adipose tissue.

When rats were exposed to a cold environment (4 degrees C) for 10 days, tissue glucose utilization was increased in brown adipose tissue (BAT), a tissue specified for non-shivering thermogenesis, but not in skeletal muscle. Cold exposure also caused an increase in the amount of GLUT4, an isoform of glucose transporters expressed in insulin-sensitive tissues, in parallel with an increased cellular level of GLUT4 mRNA. In contrast to BAT, no significant effect of cold exposure was found in skeletal muscle. The results suggest the cold-induced increase in glucose utilization by BAT is attributable, at least in part, to the increased expression of GLUT4.     

Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21

Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mRNA levels in BAT, without a concomitant increase in FGF21 plasma levels. This finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis.     

Changes in thyroid hormone and insulin status of the brown adipose tissue of cold acclimated rats on short term exposure to heat

Acclimation of rats to cold caused 45% increase in the concentration of triidothyronine (T3) and 35% increase in the concentration of thyroxine (T4) in serum. Exposure of cold-acclimated rats to heat (12 hr, 37 degrees C) failed to decrease the concentrations of thyroid hormones in circulation. The concentration of T3 in brown adipose tissue (BAT) increased almost 10-fold on cold acclimation. Iodothyronine deiodinase activity also registered 3-fold increase. Exposure of cold-acclimated animals to heat caused decrease in the concentration of T3 in BAT without appreciably affecting T4 concentration. In liver tissue, the changes in hormone concentrations were quite small compared to those in BAT. On thyroidectomy or when fed with propyl thiouracil, rats could not survive exposure to the cold. The concentration of insulin in circulation showed small increase, while that in the tissues showed significant decrease on acclimation of rats to the cold. The concentration of the hormone in BAT registered significant increase on exposure of cold-acclimated animals to heat (12 hr, 37 degrees C). The increase in liver was marginal. The temperature-dependent response of T3 indicates an important role for this hormone in rapid physiological response in BAT.     

A dramatic accumulation of glycogen in the brown adipose tissue of rats following recovery from cold exposure

In a morphological study of brown adipose tissue (BAT) of rats returned after exposure to cold (+5 degrees C) to neutral temperature (+25 degrees C), striking periodic acid Schiff staining was observed, indicating substantial glycogen accumulation. Enzymatic analysis revealed that the glycogen content increased from the 4.05 +/- 0.51 (micromol glucose unit per gram of tissue, mean +/- SE) control value to 57.3 +/- 9.66 when the animals were returned to neutral temperature for 24 h after a 1-week cold period. Glycogen repletion was also observed in liver and skeletal muscle; however, the glycogen levels in these tissues never exceeded the control values. The accumulation of glycogen in the BAT started by the 3rd hour of replacement and peaked by the 24th hour. This glycogen was readily utilized during the next short cold exposure of the animals. The plasma leptin concentration was reduced at the cold temperature. The hexokinase II activity in the BAT increased to 29.3 +/- 1.46 vs the 11.8 +/- 1.06 control (mU/mg protein +/- SE) after a 1-week cold exposure and this level was maintained during the return to neutral temperature. The total glycogen synthetase (GStot) and the glycogen synthetase a activity also increased after a 1-week cold exposure and increased further during the replacement. The level of GStot reached 26.9 +/- 1.39 vs 9.54 +/- 1.43 control by the 24th hour of replacement. At the same time, the glycogen phosphorylase a activity declined during the replacement. The concentration of glucose 6-phosphate (an activator of GS) decreased in the cold but returned to normal during the replacement. These changes in the BAT are in favor of glycogen synthesis.