| 1. |
- Barut, Inci, 1984, et al.
(författare)
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Correlative Cellular Mass Spectrometry Imaging and Amperometry Show Dose Dependent Changes in Lipid Composition and Exocytosis
- 2023
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 62:15
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant functioning of the proteasome has been associated with crucial pathologic conditions including neurodegeneration. Yet, the complex underlying causes at the cellular level remain unclear and there are conflicting reports of neuroprotective to neurodegenerative effects of proteasomal inhibitors such as lactacystin that are utilised as models for neurodegenerative diseases. The conflicting results may be associated with different dose regimes of lactacystin and hence we have performed a dose dependent study of the effects of lactacystin to identify concurrent changes in the cell membrane lipid profile and the dynamics of exocytosis using a combination of surface sensitive mass spectrometry and single cell amperometry. Significant changes of negatively charged lipids were associated with different lactacystin doses that showed a weak correlation with exocytosis while changes in PE and PE−O lipids showed dose dependent changes correlated with initial pore formation and total release of vesicle content respectively.
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| 2. |
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| 3. |
- Hatamie, Amir, et al.
(författare)
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Advances in nano/microscale electrochemical sensors and biosensors for analysis of single vesicles, a key nanoscale organelle in cellular communication
- 2023
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Ingår i: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663. ; 220
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Tidskriftsartikel (refereegranskat)abstract
- The study of subcellular targets and biochemical processes within a living cell is valuable for biological and medical research. Secretory vesicles, one such important intracellular target, are nanoscale lipid structures that are capable of storage, transport, and secretion of, for example, neurotransmitters, hormones, proteins or waste products. Vesicles play an essential role in intercellular communication systems, as they facilitate the release of chemical messaging agents. If deregulated, these communication processes can be a central part in the pathogenesis of some neurodegenerative diseases or diabetes. Generally, due to their nanometer size and intracellular location, the analysis of single vesicles and their content is a great challenge. It requires sensitive techniques, micro/nanoscale tools and sensitive instruments with extreme spatio-temporal resolution. This review focuses on electrochemical sensors to study the biochemistry and quantification of messenger molecules and other species (e.g., reactive oxygen and nitrogen species) stored in organelles, providing new trends and developments in this field. Furthermore, we review the effect of the chemical environment of single cells (e.g., treatment with chemicals, drugs, lipids, and ions) on regulation of the physical and chemical properties of vesicles. Finally, unsolved challenges of and perspectives on vesicle electroanalysis are discussed.
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| 4. |
- He, Xiulan, et al.
(författare)
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Anionic Species Regulate Chemical Storage in Nanometer Vesicles and Amperometrically Detected Exocytotic Dynamics
- 2022
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:10, s. 4310-4314
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Tidskriftsartikel (refereegranskat)abstract
- Hofmeister effects have often been ignored in living organisms, although they affect the activity and functions of biological molecules. Herein, amperometry has been applied to show that the vesicular content, dynamics of exocytosis and vesicles opening, depend on the anionic species treatment. Compared to 100 mu M Cl- treated chromaffin cells, a similar number of catecholamine molecules is released after chaotropic anions (ClO4- and SCN-) treatment, even though the vesicular catecholamine content significantly increases, suggesting a lower release fraction. In addition, there are opposite effects on the dynamics of vesicles release (shorter duration) and vesicle opening (longer duration) for chaotropic anions treated cells. Our results show aniondependent vesicle release, vesicle opening, and vesicular content, providing understanding of the pharmacological and pathological processes induced by inorganic ions.
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| 5. |
- He, Xiulan, et al.
(författare)
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Concentration of stimulant regulates initial exocytotic molecular plasticity at single cells
- 2022
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 13, s. 1815-1822
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Tidskriftsartikel (refereegranskat)abstract
- Activity-induced synaptic plasticity has been intensively studied, but is not yet well understood. We examined the temporal and concentration effects of exocytotic molecular plasticity during and immediately after chemical stimulation (30 s K+ stimulation) via single cell amperometry. Here the first and the second 15 s event periods from individual event traces were compared. Remarkably, we found that the amount of catecholamine release and release dynamics depend on the stimulant concentration. No changes were observed at 10 mM K+ stimulation, but changes observed at 30 and 50 mM (i.e., potentiation, increased number of molecules) were opposite to those at 100 mM (i.e., depression, decreased number of events), revealing changes in exocytotic plasticity based on the concentration of the stimulant solution. These results show that molecular changes initiating exocytotic plasticity can be regulated by the concentration strength of the stimulant solution. These different effects on early plasticity offer a possible link between stimulation intensity and synaptic (or adrenal) plasticity.
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| 6. |
- He, Xiulan, et al.
(författare)
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Counteranions in the Stimulation Solution Alter the Dynamics of Exocytosis Consistent with the Hofmeister Series
- 2020
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 142:29, s. 12591-12595
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Tidskriftsartikel (refereegranskat)abstract
- We show that the Hofmeister series of ions can be used to explain the cellular changes in exocytosis observed by single-cell amperometry for different counteranions. The formation, expansion, and closing of the membrane fusion pore during exocytosis was found to be strongly dependent on the counteranion species in solution. With stimulation of chaotropic anions (e.g., ClO4-), the expansion and closing time of the fusion pore are longer, suggesting chaotropes can extend the duration of exocytosis compared with kosmotropic anions (e.g., Cl-). At a concentration of 30 mM, the two parameters (e.g., t(1/2) and t(fall)) that define the duration of exocytosis vary with the Hofmeister series (Cl- < Br- < NO3- <= ClO4- < SCN-). More interestingly, fewer (e.g., N-foot/N-events) and smaller (e.g., I-foot) prespike events are observed when chaotropes are counterions in the stimulation solution, and the values can be sorted by the reverse Hofmeister series (Cl- >= Br- > NO3- > ClO4- > SCN-). Based on ion specificity, an adsorptionrepulsion mechanism, we suggest that the exocytotic Hofmeister series effect originates from a looser swelling lipid bilayer structure due to the adsorption and electrostatic repulsion of chaotropes on the hydrophobic portion of the membrane. Our results provide a chemical link between the Hofmeister series and the cellular process of neurotransmitter release via exocytosis and provide a better physical framework to understand this important phenomenon.
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| 7. |
- He, Xiulan, et al.
(författare)
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Hofmeister Series: From Aqueous Solution of Biomolecules to Single Cells and Nanovesicles
- 2023
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Ingår i: Chembiochem. - 1439-4227. ; 24:9
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Forskningsöversikt (refereegranskat)abstract
- Hofmeister effects play a critical role in numerous physicochemical and biological phenomena, including the solubility and/or accumulation of proteins, the activities of enzymes, ion transport in biochannels, the structure of lipid bilayers, and the dynamics of vesicle opening and exocytosis. This minireview focuses on how ionic specificity affects the physicochemical properties of biomolecules to regulate cellular exocytosis, vesicular content, and nanovesicle opening. We summarize recent progress in further understanding Hofmeister effects on biomacromolecules and their applications in biological systems. These important steps have increased our understanding of the Hofmeister effects on cellular exocytosis, vesicular content, and nanovesicle opening. Increasing evidence is firmly establishing that the ions along the Hofmeister series play an important role in living organisms that has often been ignored.
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| 8. |
- He, Xiulan, et al.
(författare)
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Simultaneous Counting of Molecules in the Halo and Dense-Core of Nanovesicles by Regulating Dynamics of Vesicle Opening
- 2022
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Ingår i: Angewandte Chemie-International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 61:15
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery that in the presence of chaotropic anions (SCN-) the opening of nanometer biological vesicles at an electrified interface often becomes a two-step process (around 30 % doublet peaks). We have then used this to independently count molecules in each subvesicular compartment, the halo and protein dense-core, and the fraction of catecholamine binding to the dense-core is 68 %. Moreover, we differentiated two distinct populations of large dense-core vesicles (LDCVs) and quantified their content, which might correspond to immature (43 %) and mature (30 %) LDCVs, to reveal differences in their biogenesis. We speculate this is caused by an increase in the electrostatic attraction between protonated catecholamine and the negatively charged dense-core following adsorption of SCN-.
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