Changes in mitochondrial dynamics during amyloid β-induced PC12 cell apoptosis

Changes in mitochondrial morphology and dynamics influence mitochondrial function and ultimately damage neurons in Alzheimer’s disease (AD). Amyloid β (Aβ) is a major factor in the pathogenesis of AD. Although it has been proved that Aβ can affect the dynamics of mitochondria, there is little known on the precise dynamic process. Thus, MTT, Hoechst 33342, and Annexin V/PI analysis were used to study Aβ_25–35 neurotoxity on PC12 cells, live cell station and image processing were applied to study the moving parameters and characters of mitochondria. We also studied changes of mitochondrial membrane potential and reactive oxygen species production. The results showed that long-term exposure of PC12 cells to Aβ_25–35 resulted in increase of mitochondrial number and decrease of mitochondrial length and size, which presented fluctuated during early time and dramatic changes occurred after 6 h. Low concentration exposure caused little mitochondrial changes before 24 h while short time exposure induced mitochondrial fragmentation that could be recovered to normal. Mitochondrial membrane potential dissipation and reactive oxygen species production were observed, as well as apparent cell apoptosis with significant morphological changes. These data suggest that mitochondrial fission can be reversed during Aβ_25–35-induced PC12 cell apoptosis, depending on the concentration and exposure time of Aβ_25–35, which may be helpful in AD prevention and therapy.     

Regulation of β-adrenoceptor properties and the lipid milieu in heart muscle membranes during stress

The purpose of this study was to examine changes in fatty acyl chain composition of major cardiac phospholipids in relation to down-regulation of -adrenoceptors during various forms of stress or chronic adrenergic stimulation. Analysis of the fatty acid profile of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in sarcolemma or cardiac muscle membranes showed partial replacement of 18:2n-6 by 20:4n-6 in PC and replacement of both 18:2n-6 and 20:4n-6 by 22:6n-3 in PE during daily administration of epinephrine or norepinephrine for 7 or 15 days, respectively These changes in membrane PC and PE coincided with down-regulation or the decrease in Bmax of -adrenoceptors during adrenergic stimulation. Cardiac membrane response to other forms of stress or chronic adrenergic stimulation such as neonatal stress, restriction stress or restricted food intake was expressed in the same way, that is replacement of 18:2n-6 by 20:4n-6 in PC and replacement of 18:2n-6 and 20:4n-6 by 22:6n-3 in PE.Conclusion: Adaptation to stress includes a decrease in the density of binding sites or down-regulation of -adrenoceptors in sarcolemma synchronized with specific alterations in the fatty acyl chain composition within the membrane bilayer. The changes in the lipid milieu of the membrane may facilitate conformational changes in the transmembrane segment of the receptor forming the ligand binding sites of the -adrenoceptor.     

Decreased β-adrenoceptor chronotropic response in selenium-deficient mice

With the aim to study if selenium (Se) deficiency affects the basal frequency and cardiac response to isoproterenol (ISO), mice were fed a Se-deficient diet (Se-) or the same diet supplemented with 0.2 ppm Se as sodium selenite (Se+) for 4 wk. Atria frequency, cyclic AMP (cAMP) accumulation, nitric oxide synthase (NOS) activity, and β-adrenoceptor-binding assay were then examined. Results showed that Se-mice have both a reduction in atria frequency as well as in cAMP content but higher NOS activity levels either at basal or after ISO stimulation. These differences were suppressed by feeding Se-mice with a Se-supplemented diet for 1 wk or by inhibition of inducible nitric oxide synthase (iNOS). Alterations observed after ISO stimulation in atria of Se-mice were not related to a β-adrenoceptor expression modification because specific radioligand-binding parameters in cardiac membranes from Se-mice and Se+ mice were similar. The reduced response on rate and cAMP in atria from Se-mice to direct adenylate cyclase (AC) stimulation by forskolin and the shifted upward levels present in 2-amino-4-methylpyridine-treated Se-mice is in agreement with a negative crosstalk between iNOS activity and AC activity in Se-mice.     

Changes in human γ-globulin preparations during storage

Во время хранения, человека γ-глобулин препараты протеолиза проходить медленно, в результате в составе двух фракций сплит. Один из них (γx) медленнее, чем обычно γ-глобулин, в то время как другие (γи) больше быстрыми темпами. Темпы разрушения в плазме подготовка охватывает несколько лет, тогда как в препаратов, полученных в результате haemolysed и плацентарной материала это несколько месяцев. Аналогичная разбивка была искусственно вызванной в плазмин, trypsin и papain. Определенный артикль изменения могут быть обнаружены путем immunoelectrophoresis, но электрофореза в Агар и высокоскоростного центрифугирования также дают приблизительную картину состояния подготовки. Определенный артикль γx дроби могут быть восстановлены в immunoelectrophoretically чистом состоянии путем осадков с сульфата аммония (более 50% насыщения), или с Zn₂₊ солей (в supernatant жидкости составляет более 50 мм концентрация). Определенный артикль γ_и фракция crystallizes из решений с низкой ионной силы в виде минуту, игла-как, оптически неактивных кристаллов. Причины изменений в соответствующую препаратов и биохимических и Иммунохимические аспекты с учетом явления рассматриваются.     

Arachidonic acid metabolites induced β-adrenoceptor densitization in rat lung in vitro

The possible involvement of arachidonic acid (AA) or its metabolites in β-adrenoceptor desensitization has been studied in rat lung parenchyma both from a functional and a biochemical point of view. In vitro perfusion of rat lungs with AA (3×10^?5M for 20 min) reduced the relaxant effect of isoproterenol (ISO) on lung parenchymal strips, shown by a shift to the right of ISO dose-response curve, similar to that obtained using desensitizing concentration of specific β-agonist. Moreover, AA treatment reduced the capacity of ISO to stimulate adenylate-cyclase activity, whereas the number of β-receptor binding sites was not significantly modified. Inhibition of cyclo-oxygenase pathway by indomethacin (INDO) (1.5 × 10^?5M) prevented both the loss of ISO-relaxing capacity and the decrease of adenylate-cyclase activity induced by AA treatment. In order to support the role of eicosanoids in β-adrenoceptor desensitization, changes of endogenous free AA levels have also been studied in lung homogenates. Perfusion of rat lung with ISO (10^?6M for 20 min) decreased by about 50% the levels of free AA and the pretreatment with BW755C (9×10^?5M), a lipo- and cyclo-oxygenase inhibitor, prevented this phenomenon. On the basis of these results, we suggest that the activation of AA cascade is actually involved in β-adrenoceptor desensitization in lung tissues with a possible interference at the site beyond the drug-receptor interaction.     

The Higher Structure of Chromatin in the LCR of the β-Globin Locus Changes during Development

The β-globin locus control region (LCR) is able to enhance the expression of all globin genes throughout the course of development. However, the chromatin structure of the LCR at the different developmental stages is not well defined. We report DNase I and micrococcal nuclease hypersensitivity, chromatin immunoprecipitation analyses for histones H2A, H2B, H3, and H4, and 3C (chromatin conformation capture) assays of the normal and mutant β-globin loci, which demonstrate that nucleosomes at the DNase I hypersensitive sites of the LCR could be either depleted or retained depending on the stages of development. Furthermore, MNase sensitivity and 3C assays suggest that the LCR chromatin is more open in embryonic erythroblasts than in definitive erythroblasts at the primary- and secondary-structure levels; however, the LCR chromatin is packaged more tightly in embryonic erythroblasts than in definitive erythroblasts at the tertiary chromatin level. Our study provides the first evidence that the occupancy of nucleosomes at a DNase I hypersensitive site is a developmental stage-related event and that embryonic and adult cells possess distinct chromatin structures of the LCR.     

Changes in Autoantibodies against β1-Adrenoceptor and M2-Muscarinic Receptor during Development of Renovascular Hypertension in Rats

In recent years, autoantibodies to β1-adrenoceptor andM2-muscarinic receptor have been successively discoveredin the sera of patients with dilated cardiomyopathy (DCM)[1–3] Iwata et al. [4] found that in a similar protocolwith 6-month myocardial hypertrophy, β1-adrenoceptorreceptor desensitization, increased Gi protein and G pro-tein-coupled receptor kinase-5 expression were in associ-ation with myocyte disorganization and interstitial fibrosis.So far, investigation in this field has focu…     

Changes in α- and β-amylase activities during seed germination of clover (Trifolium repens)

Changes in α- and β-amylase activities in the cotyledons of germinating clover were examined. The activity of α-amylase decreased during germination and growth of seedling, while β-amylase activity increased. These changes are different from those of germinating seeds of many other plants, but similar to the germinating seeds of alfalfa, which belongs to the same tribe (Trifolieae) as clover.     

Changes of red cell phospholipids in β-thalassemia minor

Lipid and phospholipid concentrations were determined in the red cells of β-thalassemia minor patients. A reduced concentration of total lipids and total phospholipids in red cells was found. Phosphatidylcholine and sphingomyelin were increased while phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol concentrations were decreased. These changes are similar to, though less pronounced, than those seen in β-thalassemia major. The relation of these lipids changes, free hemoglobin chains which damage the red cell membrane, and the increased rate of hemolysis is unclear.     

Changes in expression of two endogenous β-galactoside-binding isolectins in the dermis of chick embryonic skin during development in ovo and in vitro

In order to elucidate the roles of metal-independent animal lectins, we systematically investigated changes in expression of 2 kinds of -galactoside-binding isolectins (MW 14 and 16 kDa) in the dermis of chick embryonic tarsometatarsal skin during the course of development. These lectins were immunohistochemically located at different stages of development both in ovo and in vitro by light and electron microscopy. Light-microscopic observation showed that while positive staining for the 14-kDa lectin was weak at days 8 and 10 it became intense after day 13. In contrast, staining for the 16-kDa lectin was intense at days 8, 10, and 13, but it became weak after day 17 when keratinization of the epidermis was completed. Immuno-electron-microscopic observation revealed that both the 14 and 16-kDa lectins were located on the basement membrane, in the extracellular matrix, and in both the cytoplasm and the nucleus of dermal fibroblasts. Distribution of the 2 isolectins was also examined in cultured skin explants in vitro. The results were almost the same as those obtained in ovo when the skin explant was keratinized in the presence of hydrocortisone. However, in the skin explant where keratinization was prevented and mucous metaplasia was induced by the addition of vitamin A, the distribution of the 14-kDa lectin in the epidermis was significantly affected. These results indicate that (1) the expression of the 2 isolectins is differently regulated in both the dermis and epidermis, (2) the 16-kDa lectin is involved in the early stage of the formation of the dermis and the basement membrane and is replaced by the 14-kDa lectin as keratinization of the epidermis occurs, and (3) the expression of the 2 isolectins in the dermis is not significantly affected by the induction of mucous metaplasia, in contrast to their drastic changes in the epidermis.     

Mapping of Changes in EEG Spectrum Power during a Session of Biofeedback Training of the β1 Rhythm

Changes in EEG spectrum power from 19 electrode sites were studied in 19 children with attention disorders during one session of EEG–biofeedback (EEG–BFB). EEG–BFB was aimed at increasing the relative power of the ₁ rhythm (15–18 Hz) in sites Fz–C ₃ with a bipolar electrode assembly. Comparison of the EEG spectrum powers at relaxation versus training periods in one BFB session revealed significant changes in the left parasagittal frontoparietal area (F ₃, Fz, C ₃, C ₄, P ₃).     

Mitochondrial Changes in β0-Thalassemia/Hb E Disease

The compound β°-thalassemia/Hb E hemoglobinopathy is characterized by an unusually large range of presentation from essentially asymptomatic to a severe transfusion dependent state. While a number of factors are known that moderate presentation, these factors do not account for the full spectrum of presentation. Mitochondria are subcellular organelles that are pivotal in a number of cellular processes including oxidative phosphorylation and apoptosis. A mitochondrial protein enriched proteome was determined and validated from erythroblasts from normal controls and β°-thalassemia/Hb E patients of different severities. Mitochondria were evaluated through the use of mitotracker staining, analysis of relative mitochondrial genome number and evaluation of mitochondrial gene expression in addition to assay of overall cellular redox status through the use of alamarBlue assays. Fifty differentially regulated mitochondrial proteins were identified. Mitotracker staining revealed significant differences in staining between normal control erythroblasts and those from β°-thalassemia/Hb E patients. Differences in relative mitochondria number and gene expression were seen primarily in day 10 cells. Significant differences were seen in redox status as evaluated by alamarBlue staining in newly isolated CD34+ cells. Mitochondria mediate oxidative phosphorylation and apoptosis, both of which are known to be dysregulated in differentiating erythrocytes from β°-thalassemia/Hb E patients. The evidence presented here suggest that there are inherent differences in these cells as early as the erythroid progenitor cell stage, and that maximum deficit is seen coincident with high levels of globin gene expression.     

Excitatory and inhibitory responses caused by norepinephrine in duck subfornical organ neurons are mediated by β- and α 2-adrenoceptor activation

The responsiveness of spontaneously active neurons in the subfornical organ (SFO) of adult ducks to angiotensin II (ANGII), norepinephrine (NE), isoproterenol (Iso, -agonist), phenylephrine (Phe, ₁-agonist) and clonidine (Clo, ₂-agonist) was investigated in brain slices with extracellular recording technique. 64% (n=90) of the neurons increased their activity after superfusion with ANGII, the rest were unresponsive. Application of NE activated 10 and inhibited 8 neurons (n=22); the excitation being correlated with an excitatory ANGII responsiveness of the same neurons and the inhibition with the absence of an ANGII responsiveness. Iso activated 74% (n=58) and Clo inhibited 88% (n=16) of the investigated neurons. Phe did not have an effect on the majority (60%) of the neurons and produced both excitatory and inhibitory actions on the remaining cells. These results offer a plausible explanation for the dose dependent dipsogenic effect of Iso and the failure of NE to elicit dose dependent drinking, which can be explained by its dual, excitatory and inhibitory effect on SFO neurons. It is further concluded, that peripherally applied Iso exerts its dipsogenic action in high concentration by a direct excitatory effect on SFO neurons via the open blood brain barrier. Under physiological conditions, afferent neuronal input of still unknown origin might specifically modulate the activity of SFO neurons, because plasma concentrations of NE are probably not high enough to activate SFO neurons from the blood side of the blood brain barrier.Abbreviations ACSF artificial cerebrospinal fluid - ANGII angiotensin II - Clo clonidine - Iso isoproterenol - NE norepinephrine - NTS nucleus of the solitary tract - Phe phenylephrine - SFO subfornical organ     

Changes in the incidence of Down syndrome in Sweden during 1968–1982

Summary A continuous increase in the incidence of Down syndrome in Sweden was noted during 1979–1981. This increase mainly occurred among children of younger mothers and was more pronounced for hte males than for the females. There was no evidence of a significant seasonal variation, increased frequency of prematurely born children, or decrease in the number of cases aborted after prenatal diagnosis. An analysis of the whole 15-year period indicates that the incidence of Down syndrome has increased slowly in both sexes, and that there might have been a superimposed cyclic variation limited to the males.     

Changes in abscisic acid and its β-D-glucopyranosyl ester levels during tomato (Lycopersicon esculentum Mill.) seed development

Summary The role of abscisic acid (ABA) in tomato (Lycopersicon esculentum Mill.) zygotic embryogenesis was analysed. ABA and ABA ß-D-glucopyranosyl ester (ABA-GE) changes were determined in seeds and fruit tissues — placenta and mesocarp — during seed development, which was defined with eight embryo stages: from globular (stage 1) to mature embryo (stage 8). In whole seeds, ABA changes paralleled fresh and dry weight pattern curves and could be characterized by a high increase during embryo growth followed by a decrease as the seed matured and dehydrated. Moreover this dehydration phase led, at stage 8, to a new ABA distribution within the seed, preferentially into integument and embryo. Fruit tissue analyses provided new information about the ABA origin in seeds. ABA-GE levels were also measured and the results suggested different ABA metabolism in seed and fruit tissues.Abbreviations ABA abscisic acid - ABA-GE abscisic acid ß-D-glucopyranosyl ester - ABTS 2,2 — azino — bis (3 — ethylben-zthiazoline — 6 — sulfonic acid) - BHT butylhydroxytoluene - DW dry weight - ELISA Ezyme linked immunosorbent assay - HPLC high performance liquid chromatography