scholarly journals New insights into the intracellular distribution pattern of cationic amphiphilic drugs

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Magdalena Vater ◽  
Leonhard Möckl ◽  
Vanessa Gormanns ◽  
Carsten Schultz Fademrecht ◽  
Anna M. Mallmann ◽  
...  
Keyword(s):  
Distribution Pattern ◽  
Morphological Changes ◽  
Intracellular Distribution ◽  
Intact Cells ◽  
Lysosomal Compartment ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs ◽  
Intracellular Compartments ◽  
High Concentrations ◽  
First Time

Abstract Cationic amphiphilic drugs (CADs) comprise a wide variety of different substance classes such as antidepressants, antipsychotics, and antiarrhythmics. It is well recognized that CADs accumulate in certain intracellular compartments leading to specific morphological changes of cells. So far, no adequate technique exists allowing for ultrastructural analysis of CAD in intact cells. Azidobupramine, a recently described multifunctional antidepressant analogue, allows for the first time to perform high-resolution studies of CADs on distribution pattern and morphological changes in intact cells. We showed here that the intracellular distribution pattern of azidobupramine strongly depends on drug concentration and exposure time. The mitochondrial compartment (mDsRed) and the late endo-lysosomal compartment (CD63-GFP) were the preferred localization sites at low to intermediate concentrations (i.e. 1 μM, 5 μM). In contrast, the autophagosomal compartment (LC3-GFP) can only be reached at high concentrations (10 μM) and long exposure times (72 hrs). At the morphological level, LC3-clustering became only prominent at high concentrations (10 μM), while changes in CD63 pattern already occurred at intermediate concentrations (5 μM). To our knowledge, this is the first study that establishes a link between intracellular CAD distribution pattern and morphological changes. Therewith, our results allow for gaining deeper understanding of intracellular effects of CADs.

scholarly journals Erratum: Corrigendum: New insights into the intracellular distribution pattern of cationic amphiphilic drugs

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Magdalena Vater ◽  
Leonhard Möckl ◽  
Vanessa Gormanns ◽  
Carsten Schultz Fademrecht ◽  
Anna M. Mallmann ◽  
...  
Keyword(s):  
Distribution Pattern ◽  
Intracellular Distribution ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

Metformin and respiratory chain complex I: the last piece of the puzzle?

2014 ◽  
Vol 463 (3) ◽  
pp. e3-e5 ◽  
Author(s):  
Eric Fontaine
Keyword(s):  
Complex I ◽  
Chain Complex ◽  
Recent Issue ◽  
Intact Cells ◽  
Biochemical Journal ◽  
The Difference ◽  
High Concentrations ◽  
Complex I Activity ◽  
First Time

Metformin is the most widely prescribed drug used to treat patients affected by Type 2 diabetes. Metformin has also been shown to prevent some forms of cell death; however, evidence suggests that it may have anti-neoplastic properties. All of these effects have been attributed to complex I inhibition, but the mechanism by which metformin leads to complex I inhibition is not fully understood. Although it has been reported that the incubation of functionally isolated complex I in the presence of high concentrations of metformin led to its inhibition, much lower concentrations of metformin have been shown to inhibit complex I in intact cells. In a recent issue of the Biochemical Journal, Bridges, Jones, Pollak and Hirst [(2014) Biochem. J. 462, 475–487] studied for the first time the effect of metformin on purified complex I. They report that millimolar concentrations of metformin directly inhibit complex I activity in a non-competitive manner. They also specify that the binding of metformin to complex I depends on its conformation. To explain the difference in concentration required to inhibit complex I in intact cells and on isolated enzyme, Bridges et al. (2014) propose that metformin concentrates within mitochondria in intact cells. Albeit theoretically plausible, this attractive hypothesis is not directly tested by Bridges et al. (2014) Moreover, although sparse, the current literature does not support this hypothesis.

scholarly journals Morphological changes in human serum albumin in the presence of cationic amphiphilic drugs

2018 ◽  
Vol 42 (3) ◽  
pp. 2270-2277 ◽  
Author(s):  
Z. Yaseen ◽  
V. K. Aswal ◽  
X. Zhou ◽  
Kabir-ud-Din Kabir-ud-Din ◽  
S. Haider
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Morphological Changes ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

Binding of cationic amphiphilic drugs results in unfolding of human serum albumin.

Effect of verapamil on cytoplasmic distribution of granules and microfilaments in amphibian urinary bladder

1988 ◽  
Vol 46 ◽  
pp. 324-325
Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio
Keyword(s):  
Urinary Bladder ◽  
Water Flow ◽  
Morphological Changes ◽  
Granular Cell ◽  
Cytosolic Calcium ◽  
Calcium Storage ◽  
Amphibian Urinary Bladder ◽  
Vesicular Membrane ◽  
High Concentrations ◽  
Cytoskeletal System

The amphibian urinary bladder has been used as a ‘model’ system for studies of the mechanism of action of antidiuretic hormone (ADH) in stimulating transepithelial water flow. The increase in water permeability is accompanied by morphological changes that include the stimulation of apical microvilli, mobilization of microtubules and microfilaments and vesicular membrane fusion events . It has been shown that alterations in the cytosolic calcium concentrations can inhibit ADH transmembrane water flow and induce alterations in the epithelial cell cytomorphology, including the cytoskeletal system . Recently, the subapical granules of the granular cell in the amphibian urinary bladder have been shown to contain high concentrations of calcium, and it was suggested that these cytoplasmic constituents may act as calcium storage sites for intracellular calcium homeostasis. The present study utilizes the calcium antagonist, verapamil, to examine the effect of calcium deprivation on the cytomorphological features of epithelial cells from amphibian urinary bladder, with particular emphasis on subapical granule and microfilament distribution.

scholarly journals Bioactive Compounds in Salicornia patula Duval-Jouve: A Mediterranean Edible Euhalophyte

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 410
Author(s):  
Irene Sánchez-Gavilán ◽  
Esteban Ramírez ◽  
Vicenta de la Fuente
Keyword(s):  
Fatty Acids ◽  
Bioactive Compounds ◽  
Mediterranean Area ◽  
Biological Properties ◽  
Total Phenolic ◽  
Tinto River ◽  
New Findings ◽  
High Concentrations ◽  
Salicornia Patula ◽  
First Time

Many halophytes have great nutritional and functional potential, providing chemical compounds with biological properties. Salicornia patula Duval-Jouve is a common euhalophyte from saline Mediterranean territories (Spain, Portugal, France, and Italy). In the present work we quantified for the first time the bioactive compounds in S. patula (total phenolic compounds and fatty acids), from Iberian Peninsula localities: littoral-coastal Tinto River basin areas (southwest Spain, the Huelva province), and mainland continental territories (northwest and central Spain, the Valladolid and Madrid provinces). Five phenolic acids including caffeic, coumaric, veratric, salicylic, and transcinnamic have been found with differences between mainland and coastal saltmarshes. S. patula contain four flavonoids: quercetin-3-O-rutinoside, kaempferol/luteolin, apigenin 7-glucoside, and pelargonidin-3-O-rutinoside. These last two glycosylated compounds are described for the first time in this genus of Chenopodiaceae. The fatty acid profile described in S. patula stems contains palmitic, oleic, and linoleic acids in high concentrations, while stearic and long-chain fatty acids were detected in low amounts. These new findings confirm that S. patula is a valuable source of bioactive compounds from Mediterranean area.

Targeting Cancer Lysosomes with Good Old Cationic Amphiphilic Drugs

2020 ◽  
Author(s):  
Anne-Marie Ellegaard ◽  
Peter Bach ◽  
Marja Jäättelä
Keyword(s):  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

scholarly journals Association of beta-cytoplasmic actin with high concentrations of acetylcholine receptor (AChR) in normal and anti-AChR-treated primary rat muscle cultures.

1984 ◽  
Vol 32 (9) ◽  
pp. 973-981 ◽  
Author(s):  
B W Lubit
Keyword(s):  
Acetylcholine Receptor ◽  
Acetylcholine Receptors ◽  
Neuromuscular Junctions ◽  
Morphological Changes ◽  
Muscle Cells ◽  
High Concentration ◽  
Rat Muscle ◽  
Cytoplasmic Actin ◽  
High Concentrations

Previous immunocytochemical studies in which an antibody specific for mammalian cytoplasmic actin was used showed that a high concentration of cytoplasmic actin exists at neuromuscular junctions of rat muscle fibers such that the distribution of actin corresponded exactly to that of the acetylcholine receptors. Although clusters of acetylcholine receptors also are present in noninnervated rat and chick muscle cells grown in vitro, neither the mechanism for the formation and maintenance of these clusters nor the relationship of these clusters to the high density of acetylcholine receptors at the neuromuscular junction in vivo are known. In the present study, a relationship between beta-cytoplasmic actin and acetylcholine receptors in vitro has been demonstrated immunocytochemically using an antibody specific for the beta-form of cytoplasmic actin. Networks of cytoplasmic actin-containing filaments were found in discrete regions of the myotube membrane that also contained high concentrations of acetylcholine receptors; such high concentrations of acetylcholine receptors have been described in regions of membrane-substrate contact. Moreover, when primary rat myotubes were exposed to human myasthenic serum, gross morphological changes, accompanied by an apparent rearrangement of the cytoplasmic actin-containing cytoskeleton, were produced. Although whether the distribution of cytoplasmic actin-containing structures was influenced by the organization of acetylcholine receptor or vice versa cannot be determined from these studies, these findings suggest that in primary rat muscle cells grown in vitro, acetylcholine receptors and beta-cytoplasmic actin-containing structures may be somehow connected.

Interaction of Gram-Negative Bacteria with the Lysosomal Fraction of Polymorphonuclear Leukocytes II. Changes in the Cell Envelope of Escherichia coli

1970 ◽  
Vol 1 (3) ◽  
pp. 311-318
Author(s):  
D. Friedberg ◽  
I. Friedberg ◽  
M. Shilo
Keyword(s):  
Escherichia Coli ◽  
Polymorphonuclear Leukocytes ◽  
Cytoplasmic Membrane ◽  
Morphological Changes ◽  
Cell Envelope ◽  
Gram Negative Bacteria ◽  
Intact Cells ◽  
Lysosomal Fraction ◽  
E Coli ◽  
Absorbing Material

Interaction of lysosomal fraction with Escherichia coli caused damage to the cell envelope of these intact cells and to the cytoplasmic membrane of E. coli spheroplasts. The damage to the cytoplasmic membrane was manifested in the release of 260-nm absorbing material and β-galactosidase from the spheroplasts, and by increased permeability of cryptic cells to O -nitrophenyl-β- d -galactopyranoside; damage to the cell wall was measured by release of alkaline phosphatase. Microscope observation showed morphological changes in the cell envelope.

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