Search results for "serpin"

Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracain und Psicain auf die Noradrenalin-Freisetzung aus dem Herzen

1961

Die Wirkung von Reserpin auf die Konzentration von Adrenalin und Noradrenalin im Katzenherz

1959

1. Cats were given single injections of 1.8 mg/kg reserpine intraperitoneally. After a time interval of 18 hours the animals were killed. The concentration of adrenaline and noradrenaline in the right and left atria and ventricles was estimated by a method reported previously. 2. Reserpine caused a similar loss of catechol amines from all parts of the heart. The concentration of noradrenaline was reduced by 93–97%, the concentration of adrenaline by 59–79%. 3. These observations suggest that the adrenaline of the heart behaves differently from that of sympathetic ganglia or postganglionic nerve fibres after an injection of reserpine. In ganglia and nerve fibres the adrenaline concentration …

The role of cytoplasmic (newly synthesized) dopamine for the spontaneous and electrically evoked release of dopamine and its metabolites from the iso…

1987

Isolated rat NILs were incubated in Krebs-HEPES solution. The release of dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous release of the sum of metabolites was about 40 times that of dopamine. The spontaneous outflow of dopamine metabolites was unaffected after inhibition of dopamine uptake (by GBR 12921) or after pretreatment with reserpine (5 mg/kg, 12 h before the experiments), but it was reduced by 50% after preincubation with the irreversible DOPA decarboxylase inhibitor, (MFMD, 10 microM, for 10 min). The combination of pretreatment with reserpine and preincubation with MFMD resulted in an 80% inhibition of the …

Functional and dysfunctional conformers of human neuroserpin characterized by optical spectroscopies and Molecular Dynamics

2015

Neuroserpin (NS) is a serine protease inhibitor (SERPIN) involved in different neurological pathologies, including the Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), related to the aberrant polymerization of NS mutants. Here we present an in vitro and in silico characterization of native neuroserpin and its dysfunctional conformation isoforms: the proteolytically cleaved conformer, the inactive latent conformer, and the polymeric species. Based on circular dichroism and fluorescence spectroscopy, we present an experimental validation of the latent model and highlight the main structural features of the different conformers. In particular, emission spectra of aromatic res…

Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells

2013

Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents - extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiest…

Possible regulatory mechanisms responsible for the high expression of serpin protease inhibitor PI-9 in ER+ -derived breast cancer stem cells.

2015

Breast cancer (BC) is the most common endocrine cancer and the second leading cause of cancer-related death in women. About 75% of BCs expresses high levels of estrogen receptors that sustain the tumor growth. Moreover, in BC estrogens prevent apoptosis induced by granzyme B released by cytotoxic T lymphocytes and NK cells through the production of the granzyme B inhibitor PI-9. As a consequence, cancer cells acquire the ability to escape immune surveillance’s signaling. Although some studies explored the role of PI-9 in BC cells, its presence has not been investigated in cancer stem cells so far. In this research, tertiary tumorspheres were obtained from estrogen receptor-alfa positive (ER…

The necessary chances of a thermodynamically metastable protein: inactivation and polymeritzation of human neuroserpin

2009

Serpins are a wide class of proteins with high structural similarity, characterized by a unique substrate-like inhibitory mechanism that resembles a "molecular mousetrap". The active serpin is characterized by a main 5-stranded β-sheet and an exposed Reactive Centre Loop, which acts as a bait for the target protease. The cleavage of the loop by the protease triggers the insertion of the loop into the β-sheet as a strand and the disruptive translocation of the protease. This peculiar conformational mobility is achievable since serpins fold into a metastable native conformation. This feature gives a selective advantage to the serpin family to develop inhibitory activities, but leaves these pr…

Revising Ovid’s Metamorphoses: Dramatizing the Mythical in Mary Shelley’s Proserpine

2017

This contribution intends to assess the web of intertextual references in Mary Shelley’s drama Proserpine (1820), an early example of Romantic interest in revisionist mythology. The few critical efforts on the text focus on its transposition of the Ovidian narrative and its proto-feminist instances of mythical revisionism. Shelley’s adaptation primarily concerns characterization, structure and intended audience. In light of Ostriker’s (1984) suggestion that revisionist myth-making in women’s literary production constitutes a significant reshaping of shared culture and personal identity, Proserpine generally reads as a tale of defiance against patriarchal violence. The thoroughness of the ex…

Pigment epithelium-derived factor is a niche signal for neural stem cell renewal.

2006

Adult stem cells are characterized by self-renewal and multilineage differentiation, and these properties seem to be regulated by signals from adjacent differentiated cell types and by extracellular matrix molecules, which collectively define the stem cell "niche." Self-renewal is essential for the lifelong persistence of stem cells, but its regulation is poorly understood. In the mammalian brain, neurogenesis persists in two germinal areas, the subventricular zone (SVZ) and the hippocampus, where continuous postnatal neuronal production seems to be supported by neural stem cells (NSCs). Here we show that pigment epithelium-derived factor (PEDF) is secreted by components of the murine SVZ a…

Alpha-1 antitrypsin deficiency: outstanding questions and future directions

2018

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. METHODS: In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. RESULTS: 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. CONCLUSIONS: 2) Several clinical and…