Complex-formation between triphosphoinositide and experimental allergic encephalitogenic protein

1969 ◽  
Vol 111 (5) ◽  
pp. 637-646 ◽  
Author(s):  
F. B. Palmer ◽  
R. M. C. Dawson
Keyword(s):  
Sodium Chloride ◽  
Calcium Chloride ◽  
Complex I ◽  
Solvent System ◽  
Constant Composition ◽  
Complex Ii ◽  
Acidic Phospholipids ◽  
Chloroform Methanol ◽  
Experimental Allergic

1. Reactions between triphosphoinositide and the basic experimental allergic encephalitogenic (EAE) protein were examined in aqueous solution and in a biphasic solvent system (chloroform–methanol–water, 8:4:3, by vol.). 2. In the absence of salt an insoluble complex (I) is formed containing triphosphoinositide and EAE protein in proportions that represent complete neutralization of lipid and protein at the pH concerned. 3. In the presence of a low concentration (0·05m) of sodium chloride an insoluble positively charged complex (II) forms. It contains triphosphoinositide and EAE protein in a lower concentration ratio than complex I. This complex, which has a constant composition between pH7·5 and pH10, can take up additional micellar triphosphoinositide producing complex I, which can then be solubilized by excess of triphosphoinositide. 4. The complexes are dissociated by more concentrated sodium chloride solutions and low concentrations of calcium chloride, suggesting that they are largely stabilized by electrostatic bonds. The protein recovered after dissociation is immunologically active and has the same electrophoretic mobility as the original. 5. Water-insoluble ternary complexes containing triphosphoinositide, EAE protein and large amounts of phosphatidylcholine can be prepared. From these, chloroform–methanol (2:1, v/v) extracts only phosphatidylcholine. 6. An insoluble ternary complex of Ca2+ ion, EAE protein and triphosphoinositide can be prepared by adding calcium chloride to a complex I preparation solubilized by excess of triphosphoinositide. 7. EAE protein will also form complexes with other acidic phospholipids, e.g. phosphatidic acid, phosphatidylserine and phosphatidylinositol, but not with phosphatidylcholine or phosphatidylethanolamine. The phosphatidylinositol and phosphatidylserine complexes are chloroform soluble, i.e. proteolipids. 8. The possibility that complexes between EAE protein and acidic phospholipids occur in vivo is discussed. Triphosphoinositide and EAE protein occur in ox brain myelin in approximately the same concentration ratios as they do in complex II, formed at physiological salt concentration and pH.

Understanding Microdroplet Formations for Biomedical Applications

2008 ◽  
Author(s):  
Salil Desai ◽  
Anthony Moore ◽  
Benjamin Harrison ◽  
Jagannathan Sankar
Keyword(s):  
Drug Delivery ◽  
Sodium Chloride ◽  
Sodium Alginate ◽  
Calcium Chloride ◽  
Biomedical Applications ◽  
Tissue Scaffolds ◽  
Ambient Conditions ◽  
On Demand ◽  
Drop On Demand

This paper focuses on understanding microdroplet formation of sodium alginate biopolymer at various concentrations utilizing drop-on-demand inkjet technology. We investigate the effect of sodium chloride on the rheology of sodium alginate and derive a correlation between the size of the droplet versus the size of the microcapsules formed. Varying sizes of microcapsules are formed based on different concentrations of calcium chloride solvent. This understanding will give insight for fabricating drug delivery capsules and tissue scaffolds that are subject to extreme ambient conditions when interfaced with in-vivo environments.

scholarly journals ZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hayley I. Muendlein ◽  
Wilson M. Connolly ◽  
Zoie Magri ◽  
Irina Smirnova ◽  
Vladimir Ilyukha ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Complex Formation ◽  
Complex I ◽  
Yersinia Pseudotuberculosis ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Inflammatory Signaling ◽  
Complex Ii ◽  
Dependent Model

AbstractInflammation and cell death are closely linked arms of the host immune response to infection, which when carefully balanced ensure host survival. One example of this balance is the tightly regulated transition from TNFR1-associated pro-inflammatory complex I to pro-death complex II. By contrast, here we show that a TRIF-dependent complex containing FADD, RIPK1 and caspase-8 (that we have termed the TRIFosome) mediates cell death in response to Yersinia pseudotuberculosis and LPS. Furthermore, we show that constitutive binding between ZBP1 and RIPK1 is essential for the initiation of TRIFosome interactions, caspase-8-mediated cell death and inflammasome activation, thus positioning ZBP1 as an effector of cell death in the context of bacterial blockade of pro-inflammatory signaling. Additionally, our findings offer an alternative to the TNFR1-dependent model of complex II assembly, by demonstrating pro-death complex formation reliant on TRIF signaling.

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shirley Tremel ◽  
Yohei Ohashi ◽  
Dustin R. Morado ◽  
Jessie Bertram ◽  
Olga Perisic ◽  
...  
Keyword(s):  
Complex I ◽  
Kinase Domain ◽  
Beclin 1 ◽  
Structural Basis ◽  
Rab Gtpases ◽  
Lipid Kinase ◽  
Complex Ii ◽  
Cellular Processes ◽  
Specific Complex ◽  
Electron Cryotomography

AbstractThe lipid phosphatidylinositol-3-phosphate (PI3P) is a regulator of two fundamental but distinct cellular processes, endocytosis and autophagy, so its generation needs to be under precise temporal and spatial control. PI3P is generated by two complexes that both contain the lipid kinase VPS34: complex II on endosomes (VPS34/VPS15/Beclin 1/UVRAG), and complex I on autophagosomes (VPS34/VPS15/Beclin 1/ATG14L). The endosomal GTPase Rab5 binds complex II, but the mechanism of VPS34 activation by Rab5 has remained elusive, and no GTPase is known to bind complex I. Here we show that Rab5a–GTP recruits endocytic complex II to membranes and activates it by binding between the VPS34 C2 and VPS15 WD40 domains. Electron cryotomography of complex II on Rab5a-decorated vesicles shows that the VPS34 kinase domain is released from inhibition by VPS15 and hovers over the lipid bilayer, poised for catalysis. We also show that the GTPase Rab1a, which is known to be involved in autophagy, recruits and activates the autophagy-specific complex I, but not complex II. Both Rabs bind to the same VPS34 interface but in a manner unique for each. These findings reveal how VPS34 complexes are activated on membranes by specific Rab GTPases and how they are recruited to unique cellular locations.

scholarly journals Structural basis for a complex I mutation that blocks pathological ROS production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhan Yin ◽  
Nils Burger ◽  
Duvaraka Kula-Alwar ◽  
Dunja Aksentijević ◽  
Hannah R. Bridges ◽  
...  
Keyword(s):  
Point Mutation ◽  
Complex I ◽  
Structural Changes ◽  
Ischemia Reperfusion ◽  
Single Point ◽  
Structural Basis ◽  
Single Point Mutation ◽  
Ros Production

AbstractMitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia–reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the “deactive” state, usually formed only after prolonged inactivity. Despite its tendency to adopt the “deactive” state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.

SECRETION OF PROGESTERONE DURING GESTATION IN THE RAT

1978 ◽  
Vol 79 (2) ◽  
pp. 179-190 ◽  
Author(s):  
MRINAL K. SANYAL
Keyword(s):  
Abdominal Aorta ◽  
Primary Source ◽  
Solvent System ◽  
Peripheral Circulation ◽  
Systemic Circulation ◽  
Maternal Circulation ◽  
Secondary Importance ◽  
System Hexane ◽  
Venous Plasma

The concentrations of progesterone and 5α-pregnane-3,20-dione in ovarian and uterine venous plasma and in the systemic circulation were measured during gestation in the rat. The steroids were quantified by radioimmunoassay after separation on silicic acid microcolumns with the solvent system hexane: ethyl acetate (5: 2, v/v). The concentration of progesterone in the systemic circulation was highest on days 3–4 and 13–17 of pregnancy; throughout gestation, the concentration of 5α-pregnane-3,20-dione was low in relation to that of progesterone and showed no marked changes as gestation proceeded. The level of progesterone in ovarian venous effluent was 10–20 times higher than that in the uterine vein and 20–50 times greater than that in the systemic circulation. The rate of secretion of progesterone by the ovary was highest during days 13–17 of gestation and ovariectomy during this period markedly reduced the levels of progesterone in the peripheral circulation. The concentration of progesterone in the uterine venous effluent was raised compared with the concentration in plasma from the abdominal aorta, especially on days 7 and 9 of pregnancy. These results suggest that, in vivo, the rat placenta synthesizes small amounts of progesterone and secretes it into the maternal circulation. The ovary is the primary source of progesterone during pregnancy and the placental contribution is of secondary importance. Although 4-ene-5α-reductase enzyme(s) is present in the ovary and placenta, significant quantities of the reduced progestin 5α-pregnane-3,20-dione are not secreted into the systemic circulation during gestation in the rat.

Sign in / Sign up

Export Citation Format

Share Document