A Mechanism for the Inhibition of Tau Neurotoxicity: Studies with Artificial Membranes, Isolated Mitochondria, and Intact Cells

2021 ◽  
Author(s):  
Segev Naveh Tassa ◽  
Shani Ben Zichri ◽  
Shiran Lacham-Hartman ◽  
Ofek Oren ◽  
Zeev Slobodnik ◽  
...  
Keyword(s):  
Artificial Membranes ◽  
Intact Cells ◽  
Isolated Mitochondria

The mitochondrial consequences of uncoupling intact cells depend on the nature of the exogenous substrate

2001 ◽  
Vol 355 (1) ◽  
pp. 231-235 ◽  
Author(s):  
Brigitte SIBILLE ◽  
Céline FILIPPI ◽  
Marie-Astrid PIQUET ◽  
Pascale LECLERCQ ◽  
Eric FONTAINE ◽  
...  
Keyword(s):  
Oxidation Rate ◽  
Marked Decrease ◽  
Electrical Potential ◽  
Atp Synthesis ◽  
Intact Cells ◽  
Isolated Mitochondria ◽  
Exogenous Substrate ◽  
High Oxidation ◽  
Transmembrane Electrical Potential ◽  
Sustained Increase

In isolated mitochondria the consequences of oxidative phosphorylation uncoupling are well defined, whereas in intact cells various effects have been described. Uncoupling liver cells with 2,4-dinitrophenol (DNP) in the presence of dihydroxyacetone (DHA) and ethanol results in a marked decrease in mitochondrial transmembrane electrical potential (∆ψ), ATP/ADP ratios and gluconeogenesis (as an ATP-utilizing process), whereas the increased oxidation rate is limited and transient. Conversely, when DHA is associated with octanoate or proline, DNP addition results in a very large and sustained increase in oxidation rate, whereas the decreases in ∆ψ, ATP/ADP ratios and gluconeogenesis are significantly less when compared with DHA and ethanol. Hence significant energy wastage (high oxidation rate) by uncoupling is achieved only with substrates that are directly oxidized in the mitochondrial matrix. Conversely in the presence of substrates that are first oxidized in the cytosol, uncoupling results in a profound decrease in mitochondrial ∆ψ and ATP synthesis, whereas energy wastage is very limited.

Stimulation of oxygen uptake by glucagon is oxygen dependent in perfused rat liver

1989 ◽  
Vol 256 (2) ◽  
pp. G369-G376
Author(s):  
Z. Kizaki ◽  
R. G. Thurman
Keyword(s):  
Intracellular Calcium ◽  
High Flow ◽  
Perfused Liver ◽  
Normal Flow ◽  
Sprague Dawley ◽  
O2 Uptake ◽  
Intact Cells ◽  
Flow Rates ◽  
Isolated Mitochondria ◽  
Stimulation Of

Livers from well-fed female Sprague-Dawley rats (100-150 g) were perfused at flow rates of 4 or 8 ml.g liver-1.min-1 to deliver O2 to the organ at various rates. During perfusion at normal flow rates (4 ml.g-1.min-1), glucagon (10 nM) increased O2 uptake in perfused liver by approximately 40 mumol.g-1.h-1. In contrast, glucagon increased O2 uptake by nearly 100 mumol.g-1.h-1 when livers were perfused at high flow rates. Increase in O2 uptake was directly proportional to flow rate and was blocked partially by infusion of phorbol myristate acetate (100 nM) before glucagon. Increase in O2 uptake due to elevated flow was not due to enhanced glucagon delivery, since infusion of 120 nM glucagon at normal flow rates only increased O2 uptake by approximately 40 mumol.g-1.h-1. On the other hand, when O2 tension in the perfusate was manipulated at normal flow rates, the stimulation of O2 uptake by glucagon increased proportional to the average O2 tension in the liver. Infusion of 8-bromo-adenosine 3',5'-cyclic monophosphate (BrcAMP; 25 microM) also increased O2 uptake more than twice as much at high compared with normal flow rates. In the presence of angiotensin II (5 nM), a hormone that increases intracellular calcium, glucagon increased O2 uptake by nearly 100 mumol.g-1.h-1 at normal flow rates. Infusion of glucagon or BrcAMP into livers perfused at normal flow rates increased state 3 rates of O2 uptake of subsequently isolated mitochondria significantly by approximately 25%. In contrast, perfusion with glucagon or BrcAMP at high flow rates increased mitochondrial respiration by 50-60%. Glucagon addition acutely to suspensions of mitochondria, however, had no effect on O2 uptake. These data are consistent with reports that glucagon administration in vivo or treatment of intact cells with glucagon increases O2 uptake of subsequently isolated mitochondria, a phenomenon that can account for the observed increase in O2 uptake in livers perfused at high flow rates with glucagon. Furthermore, these results are consistent with the hypothesis that the effect of glucagon on mitochondria is O2 dependent in the perfused liver. This is most likely due to an effect of intracellular calcium on a mechanism mediated via cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals THE STRUCTURE OF SOME CYTOPLASMIC COMPONENTS OF PLANT CELLS IN RELATION TO THE BIOCHEMICAL PROPERTIES OF ISOLATED PARTICLES

1957 ◽  
Vol 3 (1) ◽  
pp. 61-70 ◽  
Author(s):  
A. J. Hodge ◽  
E. M. Martin ◽  
R. K. Morton
Keyword(s):  
Endoplasmic Reticulum ◽  
Wheat Root ◽  
Dense Material ◽  
Animal Cells ◽  
Wheat Roots ◽  
Root Cells ◽  
Intact Cells ◽  
Thin Sections ◽  
Isolated Mitochondria ◽  
Silver Beet

1. Electron micrographs of thin sections of material fixed with buffered osmium tetroxide have been used for comparison of the fine structure of isolated cytoplasmic particles from silver beet petioles and roots of germinating wheat with that of the cytoplasm of the intact cells. 2. Mitochondria of wheat roots have an external double membrane and poorly oriented internal double membranes. As compared with the structures seen in situ, the isolated mitochondria showed evidence of some disorganisation of the fine internal structure, probably due to osmotic effects. The possible influence of such changes on the enzymic properties of the isolated mitochondria is discussed. 3. The isolated plant microsomes are mainly spherical vesicular structures consisting of (a) an outer membrane enclosing (b) either an homogeneous slightly dense material (wheat root microsomes) or some granular dense material (silver beet microsomes) and (c) small dense particles, mostly associated with the vesicle membranes. 4. The cytoplasm of the wheat root cells does not contain any structures similar to the isolated microsomes but has a very dense reticular network, consisting of membranes with associated small dense particles, here called the endoplasmic reticulum. The observations indicate that the isolated microsomes arise mainly by rupture and transformation of the membranes of this structure. The effects of such extensive changes in the lipoprotein membranes on the enzymic activities of the endoplasmic reticulum, as studied in isolated microsomes, is discussed. 5. Meristematic wheat root cells contain structures which consist of smooth membranes with associated vacuoles and are similar to the Golgi zones of animal cells. The membranes of these zones probably contribute to the microsomal fraction under the conditions of preparation used for the enzymic and chemical studies previously reported.

Effects of protamine and strophanthin on mitochondrial potassium, sodium and water

1960 ◽  
Vol 199 (4) ◽  
pp. 653-656
Author(s):  
Leonard Share
Keyword(s):  
Rat Liver ◽  
Sodium Concentration ◽  
Water Metabolism ◽  
Intact Cells ◽  
Kidney Mitochondria ◽  
Potassium Sodium ◽  
Isolated Mitochondria ◽  
Liver And Kidney ◽  
Uncoupling Of Oxidative Phosphorylation ◽  
High Concentrations

A study was made of the effects of certain agents, which inhibit potassium transport in intact cells, on the potassium, sodium and water metabolism of isolated mitochondria. Protamine (4 mg/100 ml) induced swelling in rat liver and kidney mitochondria and impaired the ability of these mitochondria to concentrate potassium. These actions appeared to be associated with the uncoupling of oxidative phosphorylation. Protamine was without effect on the mitochondrial sodium concentration. Strophanthin at extremely high concentrations (1 gm/100 ml) was also found to induce swelling of rat liver, kidney and heart mitochondria and to interfere with the ability of the mitochondria to concentrate potassium. There was a tendency for mitochondrial sodium concentration to be elevated. It is concluded that the actions of protamine and strophanthin on mitochondria are qualitatively and quantitatively different from the actions of these substances on intact cells and that there are basic differences between the potassium concentrating mechanisms in mitochondria and in intact cells.

Mitochondrial control of apoptosis: an overview

1999 ◽  
Vol 66 ◽  
pp. 1-15 ◽  
Author(s):  
Guido Kroemer
Keyword(s):  
Transmembrane Potential ◽  
Mitochondrial Permeability Transition ◽  
Ion Selectivity ◽  
Permeability Transition ◽  
Critical Event ◽  
Intact Cells ◽  
Isolated Mitochondria ◽  
Pore Opening ◽  
Mitochondrial Megachannel

The mitochondrial permeability transition (PT) pore, also called the mitochondrial megachannel, is a multiprotein complex formed at the contact site between the mitochondrial inner and outer membranes, exactly the same location at which Bax, Bcl-2 and Bcl-XL are particularly abundant. The PT pore participates in the regulation of matrix Ca2+, pH, transmembrane potential and volume, and functions as a Ca2+-, voltage-, pH- and redox-gated channel with several levels of conductance and little, if any, ion selectivity. We have obtained three independent lines of evidence implicating the mitochondrial PT pore in apoptosis. First, in intact cells, apoptosis is accompanied by an early dissipation of the mitochondrial transmembrane potential, ΔΨm. In several models of apoptosis, specific agents inhibiting the mitochondrial PT pore abolish this dissipation of the ΔΨm and simultaneously prevent activation of downstream caspases and endonucleases, indicating that PT pore opening can be a critical event of the apoptotic process. Secondly, mitochondria are rate-limiting for caspase and nuclease activation in several cell-free systems of apoptosis. Isolated mitochondria release apoptogenic factors capable of activating pro-caspases or endonucleases upon opening of the mitochondrial megachannel in vitro. Thirdly, opening of the purified PT pore complex reconstituted into liposomes is inhibited by recombinant Bcl-2 or Bcl-XL, two apoptosis-inhibitory proteins that also prevent PT pore opening in cells and isolated mitochondria. Altogether, our results suggest that PT pore opening is sufficient and (mostly) necessary for triggering apoptosis. The implications of these findings are examined in the light of pharmacological interventions in apoptosis.

Interactions of Chloromethyltetramethylrosamine (Mitotracker Orangetm) with Isolated Mitochondria and Intact Cells

1999 ◽  
Vol 893 (1 OXIDATIVE/ENE) ◽  
pp. 391-395 ◽  
Author(s):  
LUCA SCORRANO ◽  
VALERIA PETRONILLI ◽  
RAFFAELE COLLONA ◽  
FABIO DI LISA ◽  
PAOLO BERNARDI
Keyword(s):  
Intact Cells ◽  
Isolated Mitochondria

scholarly journals Oxygen affinity of the respiratory chain of Acanthamoeba castellanii

1983 ◽  
Vol 214 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D Lloyd ◽  
H Mellor ◽  
J L Williams
Keyword(s):  
Plasma Membrane ◽  
Cytochrome C ◽  
Cytochrome B ◽  
Respiratory Chain ◽  
Oxygen Affinity ◽  
Acanthamoeba Castellanii ◽  
Intact Cells ◽  
Cytochrome Aa3 ◽  
Isolated Mitochondria ◽  
Soil Amoeba

Apparent Km values for O2 for the soil amoeba Acanthamoeba castellanii determined polarographically and by bioluminescence gave similar values (0.37 and 0.41 microM respectively). Mitochondria oxidizing succinate or NADH in the presence or absence of ADP gave values in the range 0.21-0.36 microM-O2. Oxidation of respiratory-chain components to 50% of the aerobic steady states in intact cells was observed at the following O2 concentrations: cytochrome aa3, 0.1-0.25 microM; cytochrome c, 0.3-0.6 microM; cytochrome b, 0.35-0.45 microM; flavoprotein, 2 microM. In isolated mitochondria corresponding values for a-, c- and b-type cytochromes were 0.007, 0.035-0.05 and 0.06-0.09 microM-O2. It is concluded that an O2 gradient exists between plasma membrane and mitochondria in A. castellanii.

Inhibition of mitochondrial oxidative metabolism by SKF-525a in intact cells and isolated mitochondria

1983 ◽  
Vol 32 (22) ◽  
pp. 3285-3295 ◽  
Author(s):  
Tommaso Galeotti ◽  
Maria-Luisa Eboli ◽  
Guglielmo Palombini ◽  
George D.V. van Rossum ◽  
Shiv C. Kapoor
Keyword(s):  
Oxidative Metabolism ◽  
Intact Cells ◽  
Isolated Mitochondria ◽  
Mitochondrial Oxidative Metabolism

scholarly journals Malate exchange between the cytosol and mitochondria

1973 ◽  
Vol 132 (2) ◽  
pp. 349-352 ◽  
Author(s):  
Robert Rognstad ◽  
Joseph Katz
Keyword(s):  
Transport System ◽  
Isotopic Exchange ◽  
Phosphate Transport ◽  
Effective Inhibitor ◽  
Intact Cells ◽  
Isolated Mitochondria ◽  
Potential Inhibitors

1. By comparing the relative isotopic yields in glucose and CO2 from precursors of mitochondrial and cytosolic malate, it is evident that the rate of isotopic exchange between these compartments is rapid. 2. A variety of potential inhibitors of malate exchange were tested, but no specific and effective inhibitor of the isotopic exchange has been found. 3. Compounds such as n-butylmalonate and p-iodobenzylmalonate, which have been used as inhibitors of the malate–phosphate transport system in isolated mitochondria, do not appear to be sufficiently specific to be useful in studies with intact cells.

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