Neuronal Formation of Free Radicals Plays a Minor Role in Hypoxic Cell Death in Human NT2-N Neurons

Growth and survival of hematopoietic cells is regulated by growth factors and cytokines, such as interleukin 3 (IL-3). When cytokine is removed, cells dependent on IL-3 kill themselves by a mechanism that is inhibited by overexpression of Bcl-2 and is likely to be mediated by proapoptotic Bcl-2 family members. Bad and Bim are 2 such BH3-only Bcl-2 family members that have been implicated as key initiators in apoptosis following growth factor withdrawal, particularly in IL-3-dependent cells. To test the role of Bad, Bim, and other proapoptotic Bcl-2 family members in IL-3 withdrawal-induced apoptosis, we generated IL-3-dependent cell lines from mice lacking the genes for Bad, Bim, Puma, both Bad and Bim, and both Bax and Bak. Surprisingly, Bad was not required for cell death following IL-3 withdrawal, suggesting changes to phosphorylation of Bad play only a minor role in apoptosis in this system. Deletion of Bim also had no effect, but cells lacking Puma survived and formed colonies when IL-3 was restored. Inhibition of the PI3 kinase pathway promoted apoptosis in the presence or absence of IL-3 and did not require Bad, Bim, or Puma, suggesting IL-3 receptor survival signals and PI3 kinase survival signals are independent.

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Mechanisms of cell death in diabetes: A minor role for CD95

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.95.23.13818 ◽

1998 ◽

Vol 95 (23) ◽

pp. 13818-13822 ◽

Cited By ~ 70

Author(s):

J. Allison ◽

A. Strasser

Keyword(s):

Cell Death ◽

Minor Role ◽

A Minor

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Involvement of Caspase-3 in Cell Death after Hypoxia–Ischemia Declines during Brain Maturation

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200009000-00003 ◽

2000 ◽

Vol 20 (9) ◽

pp. 1294-1300 ◽

Cited By ~ 246

Author(s):

Bing R. Hu ◽

Chun Li Liu ◽

Yibing Ouyang ◽

Klas Blomgren ◽

Bo K. Siesjö

Keyword(s):

Cell Death ◽

Caspase 3 ◽

Brain Maturation ◽

Minor Role ◽

Artery Ligation ◽

Adult Rats ◽

Hypoxia Ischemia ◽

High Level ◽

A Minor ◽

Active Caspase

The involvement of caspase-3 in cell death after hypoxia–ischemia (HI) was studied during brain maturation. Unilateral HI was produced in rats at postnatal day 7 (P7), 15 (P15), 26 (P26), and 60 (P60) by a combination of left carotid artery ligation and systemic hypoxia (8% O2). Activation of caspase-3 and cell death was examined in situ by high-resolution confocal microscopy with anti-active caspase-3 antibody and propidium iodide and by biochemical analysis. The active caspase-3 positive neurons were composed of more than 90% HI damaged striatal and neocortical neurons in P7 pups, but that number was reduced to approximately 65% in striatum and 34% in the neocortex of P15 pups, and approximately 26% in striatum and 2% in neocortex of P26 rats. In P60 rats, less than 4% of the damaged neurons in striatum and less than 1% in neocortex were positive for active caspase-3. Western blot analysis demonstrated that the level of inactive caspase-3 in normal forebrain tissue gradually declined from a high level in young pups to very low levels in adult rats. Concomitantly, HI-induced active caspase-3 was reduced from a relatively high level in P7, to moderate levels in P15 and P26, to a barely detectable level in P60 rats. The authors conclude that the involvement of caspase-3 in the pathogenesis of cell death after HI declines during neuronal maturation. The authors hypothesize that caspase-3 may play a major role in cell death in immature neurons but a minor role in cell death in mature neurons after brain injury.

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Electrostatic interactions play a minor role in the binding of ExoS to 14-3-3 proteins

Biochemical Journal ◽

10.1042/bj20100043 ◽

2010 ◽

Vol 427 (2) ◽

pp. 217-224 ◽

Cited By ~ 8

Author(s):

Lubna Yasmin ◽

Jeffrey L. Veesenmeyer ◽

Maureen H. Diaz ◽

Matthew S. Francis ◽

Christian Ottmann ◽

...

Keyword(s):

Cell Death ◽

Electrostatic Interaction ◽

Interaction Potential ◽

Stress Responses ◽

Electrostatic Interactions ◽

Cell Metabolism ◽

Structural Basis ◽

Minor Role ◽

Secondary Importance ◽

A Minor

14-3-3 proteins belong to a family of conserved molecules expressed in all eukaryotic cells that play an important role in a multitude of signalling pathways. 14-3-3 proteins bind either to phosphoserine/phosphothreonine residues or to sequence-specific non-phosphorylated motifs in more than 200 interaction partners [Pozuelo Rubio, Geraghty, Wong, Wood, Campbell, Morrice and Mackintosh (2004) Biochem. J. 379, 395–408]. These interactions result in cell-cycle regulation, apoptosis, stress responses, cell metabolism and malignant transformation. One example of a phosphorylation-independent interaction is the binding of 14-3-3 to ExoS (exoenzyme S), a bacterial ADP-ribosyltransferase toxin of Pseudomonas aeruginosa. In the present study, we have utilized additional biochemical and infection analyses to define further the structural basis of the interaction between ExoS and 14-3-3. An ExoS leucine-substitution mutant dramatically reduced the interaction potential with 14-3-3 suggesting that Leu422, Leu423, Leu426 and Leu428 of ExoS are important for its interaction with 14-3-3, its enzymatic activity and cytotoxicity. However, ExoS substitution mutants of residues that interact with 14-3-3 through an electrostatic interaction, such as Ser416, His418, Asp424 and Asp427, showed no reduction in their interaction potential with 14-3-3. These ExoS substitution mutants were also as aggressive as wild-type ExoS at inducing cell death and to modify endogenous ExoS target within the cell. In conclusion, electrostatic interaction between ExoS and 14-3-3 via polar residues (Ser416, His418, Asp424 and Asp427) appears to be of secondary importance. Thus the interaction between the ‘roof’ of the groove of 14-3-3 and ExoS relies more on hydrophobic interaction forces, which probably contributes to induce cell death after ExoS infection and activation.

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The Effect of Path Length and Display Size on Memory for Spatial Information

Experimental Psychology (formerly Zeitschrift für Experimentelle Psychologie) ◽

10.1027/1618-3169/a000137 ◽

2012 ◽

Vol 59 (3) ◽

pp. 147-152 ◽

Cited By ~ 11

Author(s):

Katherine Guérard ◽

Sébastien Tremblay

Keyword(s):

Path Length ◽

Potential Role ◽

Spatial Information ◽

Recall Performance ◽

Minor Role ◽

Length Effect ◽

Serial Memory ◽

Fixed Reference ◽

A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

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Use of Different Tissue Thromboplastins in the Control of Anticoagulant-Therapy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656198 ◽

1958 ◽

Vol 02 (05/06) ◽

pp. 462-480 ◽

Cited By ~ 1

Author(s):

Marc Verstraete ◽

Patricia A. Clark ◽

Irving S. Wright

Keyword(s):

Prothrombin Time ◽

Anticoagulant Therapy ◽

Factor Vii ◽

Rabbit Brain ◽

Minor Role ◽

Rabbit Lung ◽

Coagulation Mechanism ◽

Time Test ◽

The One ◽

A Minor

SummaryAn analysis of the results of prothrombin time tests with different types of thromboplastins sheds some light on the problem why the administration of coumarin is difficult to standardize in different centers. Our present ideas on the subject, based on experimental data may be summarized as follows.Several factors of the clotting mechanism are influenced by coumarin derivatives. The action of some of these factors is by-passed in the 1-stage prothrombin time test. The decrease of the prothrombin and factor VII levels may be evaluated in the 1-stage prothrombin time determination (Quick-test). The prolongation of the prothrombin times are, however, predominantly due to the decrease of factor VII activity, the prothrombin content remaining around 50 per cent of normal during an adequate anticoagulant therapy. It is unlikely that this degree of depression of prothrombin is of major significance in interfering with the coagulation mechanism in the protection against thromboembolism. It may, however, play a minor role, which has yet to be evaluated quantitatively. An exact evaluation of factor VII is, therefore, important for the guidance of anticoagulant therapy and the method of choice is the one which is most sensitive to changes in factor VII concentration. The 1-stage prothrombin time test with a rabbit lung thromboplastin seems the most suitable method because rabbit brain preparations exhibit a factor VII-like activity that is not present in rabbit lung preparations.

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Produktivkraft als Versprechen

PROKLA Zeitschrift für kritische Sozialwissenschaft ◽

10.32387/prokla.v46i185.135 ◽

2016 ◽

Vol 46 (185) ◽

pp. 621-638 ◽

Cited By ~ 3

Author(s):

Christian Siefkes

Keyword(s):

Private Consumption ◽

Minor Role ◽

Progressive Reduction ◽

Internal Forces ◽

A Minor

The ‘Fragment on Machines’ from Marx’s Grundrisse is often cited as an argument that the internal forces of capitalism will lead to its doom. But the argument that the progressive reduction of labor must doom capitalism lacks a proper foundation, as a comparison with the ‘Schemes of Reproduction’ given in Capital II shows. The latter, however, aren’t fully convincing either. In reality, more depends on the private consumption of capitalists than either model recognizes. Ultimately, most can be made of the ‘Fragment on Machines’ by reading it not as an exposure of capitalism’s internal contractions, but as a discussion of a possible communist future where labor (or work) will play but a minor role.

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Effects of Myo-inositol Alone and in Combination with Seleno-Lmethionine on Cadmium-Induced Testicular Damage in Mice

Current Molecular Pharmacology ◽

10.2174/1874467212666190620143303 ◽

2019 ◽

Vol 12 (4) ◽

pp. 311-323 ◽

Cited By ~ 3

Author(s):

Salvatore Benvenga ◽

Antonio Micali ◽

Giovanni Pallio ◽

Roberto Vita ◽

Consuelo Malta ◽

...

Keyword(s):

Structural Changes ◽

Natural Antioxidants ◽

Minor Role ◽

Positive Role ◽

Testosterone Levels ◽

Tnf Α ◽

Testicular Lesions ◽

A Minor ◽

Immunohistochemical Analyses

Background: Cadmium (Cd) impairs gametogenesis and damages the blood-testis barrier. Objective: As the primary mechanism of Cd-induced damage is oxidative stress, the effects of two natural antioxidants, myo-inositol (MI) and seleno-L-methionine (Se), were evaluated in mice testes. Methods: Eighty-four male C57 BL/6J mice were divided into twelve groups: 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); Se (0.2 mg/kg/day per os); Se (0.4 mg/kg/day per os); MI (360 mg/kg/day per os); MI plus Se (0.2 mg/kg/day); MI plus Se (0.4 mg/kg/day); CdCl2 (2 mg/kg/day i.p.) plus vehicle; CdCl2 plus MI; CdCl2 plus Se (0.2 mg/kg/day); CdCl2 plus Se (0.4 mg/kg/day); CdCl2 plus MI plus Se (0.2 mg/kg/day); and CdCl2 plus MI plus Se (0.4 mg/kg/day). After 14 days, testes were processed for biochemical, structural and immunohistochemical analyses. Results: CdCl2 increased iNOS and TNF-α expression and Malondialdehyde (MDA) levels, lowered glutathione (GSH) and testosterone, induced testicular lesions, and almost eliminated claudin-11 immunoreactivity. Se administration at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression, maintained GSH, MDA and testosterone levels, structural changes and low claudin-11 immunoreactivity. MI alone or associated with Se at 0.2 or 0.4 mg/kg significantly reduced iNOS and TNF-α expression and MDA levels, increased GSH and testosterone levels, ameliorated structural organization and increased claudin-11 patches number. Conclusion: We demonstrated a protective effect of MI, a minor role of Se and an evident positive role of the association between MI and Se on Cd-induced damages of the testis. MI alone or associated with Se might protect testes in subjects exposed to toxicants, at least to those with behavior similar to Cd.

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Extraction of strontium and barium salts by the nitrobenzene solution of dicarbolide in the presence of glymes

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19850581 ◽

1985 ◽

Vol 50 (3) ◽

pp. 581-599 ◽

Cited By ~ 41

Author(s):

Petr Vaňura ◽

Emanuel Makrlík

Keyword(s):

Stability Constants ◽

Organic Phase ◽

Equilibrium Constants ◽

Minor Role ◽

Nitrobenzene Solution ◽

Ligand Structure ◽

Stability Constants Of Complexes ◽

Separation Factors ◽

The Stability ◽

A Minor

Extraction of microamounts of Sr2+ and Ba2+ (henceforth M2+) from the aqueous solutions of perchloric acid (0.0125-1.02 mol/l) by means of the nitrobenzene solutions of dicarbolide (0.004-0.05 mol/l of H+{Co(C2B9H11)2}-) was studied in the presence of monoglyme (only Ba2+), diglyme, triglyme, and tetraglyme (CH3O-(CH2-CH2O)nCH3, where n = 1, 2, 3, 4). The distribution of glyme betweeen the aqueous and organic phases, the extraction of the protonized glyme molecule HL+ together with the extraction of M2+ ion and of the glyme complex with the M2+ ion, i.e., ML2+ (where L is the molecule of glyme), were found to be the dominating reactions in the systems under study. In the systems with tri- and tetraglymes the extraction of H+ and M2+ ions solvated with two glyme molecules, i.e., the formation of HL2+ and ML22+ species, can probably play a minor role. The values of the respective equilibrium constants, of the stability constants of complexes formed in the organic phase, and the theoretical separation factors αBa/Sr were determined. The effect of the ligand structure on the values of extraction and stability constants in the organic phase is discussed.

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The preendosomal compartment comprises distinct coated and noncoated endocytic vesicle populations.

The Journal of Cell Biology ◽

10.1083/jcb.113.4.731 ◽

1991 ◽

Vol 113 (4) ◽

pp. 731-741 ◽

Cited By ~ 50

Author(s):

S H Hansen ◽

K Sandvig ◽

B van Deurs

Keyword(s):

Cell Surface ◽

Coated Vesicles ◽

Minor Role ◽

Specific Marker ◽

Con A ◽

Early Endosomes ◽

Gold Conjugate ◽

Entire Cell ◽

A Minor ◽

Endocytic Vesicles

The transfer of molecules from the cell surface to the early endosomes is mediated by preendosomal vesicles. These vesicles, which have pinched off completely from the plasma membrane but not yet fused with endosomes, form the earliest compartment along the endocytic route. Using a new assay to distinguish between free and cell surface connected vesicle profiles, we have characterized the preedosomal compartment ultrastructurally. Our basic experimental setup was labeling of the entire cell surface at 4 degrees C with Con A-gold, warming of the cells to 37 degrees C to allow endocytosis, followed by replacing incubation medium with fixative, all within either 30 or 60 s. Then the fixed cells were incubated with anti-Con A-HRP to distinguish truly free (gold labeled) endocytic vesicles from surface-connected structures. Finally, analysis of thin (20-30 nm) serial sections and quantification of vesicle diameters were carried out. Based on this approach it is shown that the preendosomal compartment comprises both clathrin-coated and non-coated endocytic vesicles with approximately the same frequency but with distinct diameter distributions, the average noncoated vesicle being smaller (95 nm) than the average coated one (110 nm). In parallel experiments, using an anti-transferrin receptor gold-conjugate as a specific marker for clathrin-dependent endocytosis it is also shown that uncoating of coated vesicles plays only a minor role for the total frequency of noncoated vesicles. Furthermore, after perturbation of clathrin-dependent endocytosis by potassium depletion where uptake of transferrin is blocked, noncoated endocytic vesicles with Con A-gold, but not coated vesicles, exist already after 30 and 60 s. Finally, it is shown that the existence of small, free vesicles in the short-time experiments cannot be ascribed to recycling from the early endosomes.

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