The active role of Ca2+ ions in Aβ-mediated membrane damage

2018 ◽  
Vol 54 (29) ◽  
pp. 3629-3631 ◽  
Author(s):  
Michele F. M. Sciacca ◽  
Irene Monaco ◽  
Carmelo La Rosa ◽  
Danilo Milardi
Keyword(s):  
Calcium Ions ◽  
Membrane Damage ◽  
Active Role ◽  
Membrane Disruption ◽  
Induced Membrane ◽  
Membrane Poration

Calcium ions inhibits Aβ induced membrane poration by small-sized oligomers but significantly foster fiber-dependent membrane disruption.

scholarly journals Keeping α-Synuclein at Bay: A More Active Role of Molecular Chaperones in Preventing Mitochondrial Interactions and Transition to Pathological States?

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 289
Author(s):  
Emelie E. Aspholm ◽  
Irena Matečko-Burmann ◽  
Björn M. Burmann
Keyword(s):  
Molecular Chaperones ◽  
Mitochondrial Membrane ◽  
Structural Transition ◽  
Current Knowledge ◽  
Lewy Bodies ◽  
Protein Aggregates ◽  
Active Role ◽  
Proteolytic Processing ◽  
Membrane Disruption

The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation of Lewy bodies, intracellular inclusions containing protein aggregates as well as broken organelles found in the brains of Parkinson’s patients. In parallel, a short motif around Tyr39 was identified as being crucial for the aggregation of α-synuclein. Interestingly, this region is also one of the main segments in contact with a diverse pool of molecular chaperones. Further, it could be shown that the inhibition of the chaperone:α-synuclein interaction leads to a binding of α-synuclein to mitochondria, which could also be shown to lead to mitochondrial membrane disruption as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases. Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading to enhanced mitochondrial interaction and consequential mitochondrial breakage, which might mark the initial stages of the structural transition of α-synuclein towards its pathological states.

scholarly journals Enhancement of Heme-Induced Membrane Damage by the Anti-malarial Clotrimazole: the Role of Colloid-Osmotic Forces

2004 ◽  
Vol 27 (3) ◽  
pp. 361-365 ◽  
Author(s):  
Nguyen Tien Huy ◽  
Ryo Takano ◽  
Saburo Hara ◽  
Kaeko Kamei
Keyword(s):  
Membrane Damage ◽  
Induced Membrane

The Lipid-Chaperon Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins

2020 ◽  
Author(s):  
Michele F. M. Sciacca ◽  
Fabio Lolicato ◽  
Carmelo Tempra ◽  
Federica Scollo ◽  
Bikash R. Sahoo ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Membrane Damage ◽  
Amyloid Β ◽  
Disordered Proteins ◽  
Amyloid Formation ◽  
Intrinsically Disordered ◽  
Molecular Events ◽  
Membrane Poration ◽  
Synuclein Proteins

<p>Increasing number of human diseases have been shown to be linked to aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, and α-synuclein are, indeed, involved in type-II diabetes, Alzheimer’s, and Parkinson’s, respectively. Despite the correlation of the toxicity of these proteins at early aggregation stages with membrane damage, the molecular events underlying the process is quite complex to understand. In this study, we demonstrate the crucial role of free lipids in the formation of lipid-protein complex, which enables an easy membrane insertion for amylin, amyloid-β, and α-synuclein. Experimental results from a variety of biophysical methods and molecular dynamics results reveal this common molecular pathway in membrane poration is shared by amyloidogenic (amylin, amyloid-β, and α-synuclein) and non-amyloidogenic (rat IAPP, β-synuclein) proteins. Based on these results, we propose a “lipid-chaperone” hypothesis as a unifying framework for protein-membrane poration.<b></b></p>

Role of water and electrolyte influxes in anoxic plasma membrane disruption

1997 ◽  
Vol 273 (4) ◽  
pp. C1341-C1348 ◽  
Author(s):  
Jing Chen ◽  
Lazaro J. Mandel
Keyword(s):  
Plasma Membrane ◽  
Proximal Tubule ◽  
Plasma Membranes ◽  
Membrane Disruption ◽  
Hypertonic Medium ◽  
Great Capacity ◽  
Induced Membrane ◽  
Water Influx ◽  
Response To Water

The role of water and electrolyte influxes in anoxia-induced plasma membrane disruption was investigated using rabbit proximal tubule suspension. The results indicated that normal proximal tubule (PT) cells have a great capacity for expanding cell volume in response to water influx, whereas anoxia increases the susceptibility to water influx-induced disruption, and this was attenuated by glycine. However, resistance of anoxic plasma membranes to water influx-induced stress is not lost, although their mechanical strength was diminished, compared with normoxic membranes. Anoxic membranes did not disrupt under an intra-to-extracellular osmotic difference as great as 150 mosM. Potentiating or attenuating water influx by incubating PT cells in hypotonic or hypertonic medium, respectively, during anoxia, did not affect anoxia-induced membrane disruption. After the transmembrane electrolyte concentration gradient was eliminated by a “intracellular” buffer or by permeabilizing the plasma membrane to molecules <4 kDa using α-toxin, anoxia still caused further membrane disruption that was prevented by glycine or low pH. These results demonstrate that 1) water or net electrolyte influxes are probably not a primary cause for anoxia-induced membrane disruption and 2) glycine could prevent the plasma membrane disruption during anoxia independently from its effect on transmembrane electrolyte or water influxes. The present data support a biochemical rather than a mechanical alteration of the plasma membrane as the underlying cause of membrane disruption during anoxia.

scholarly journals AMELIORATIVE ROLE OF GARLIC (ALLIUM SATIVUM) ON CHROMIUM (VI) - INDUCED MEMBRANE DAMAGE IN MALE ALBINO RATS

2021 ◽  
pp. 69-72
Author(s):  
SOUMITA DEY ◽  
SANKAR KUMAR DEY
Keyword(s):  
Body Weight ◽  
Plasma Membrane ◽  
Aqueous Extract ◽  
Membrane Damage ◽  
The Body ◽  
Albino Rats ◽  
Treatment Schedule ◽  
Induced Membrane ◽  
Liver And Kidney

Objective: Membrane damage is one of the important consequences of chromium (Cr) induced cytotoxicity. Garlic possesses antioxidant property to scavenge the toxic radicals and cytoprotective activity. The aim of the present study is to evaluate the ameliorative role of aqueous extract of garlic (AEG) on Cr-induced membrane damage of both liver and kidneys in male albino rats. Methods: Male albino rats of Wistar strain (80-100 g) were used for the present study. Rats were divided into three groups of almost equal average body weight. The animals of two groups were injected K2Cr2O7 at a dose of 0.8 mg per 100 g body weight per day for 28 days. The animals of one of the Cr-treated groups served as the supplemented group supplied aqueous extract of garlic (AEG) (250 mg per kg body weight daily at an interval of 6 h after injection of Cr for a period of 28 days). The animals of the remaining group received only the vehicle (0.9% NaCl), served as control. The body weights of the animals were taken in each day of treatment schedule. Results: The results indicated that significant increases in membrane cholesterol level as well as significant decreases in membrane phospholipid level in Cr exposed animals suggest structural alterations in both liver and kidneys plasma membrane. Alkaline phosphatase (ALP), total ATPase, and Na+-K+- ATPase activities of plasma membrane were significantly decreased in both liver and kidneys after Cr treatment. On the other hand, AEG supplementation plays a vital role to restore such alterations induced by Cr in plasma membrane of both liver and kidney. Conclusion: These findings indicate that Cr treatment at the present dose and duration induces structural and functional alterations in the plasma membrane in both liver and kidney. However, AEG supplementation restored those alterations induced by Cr in plasma membrane of both liver and kidneys but was not able to eliminate the deposited Cr from the liver and kidney tissues.

Membrane Integrity as a Therapeutic Target in Neural Cell Injury

2004 ◽  
Author(s):  
Kenneth A. Barbee ◽  
Gulyeter Serbest ◽  
Joel Horwitz
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Membrane Disruption ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Post Injury

The importance of cell membrane integrity for normal cell function and indeed survival is well established, yet the role of membrane disruption in cellular pathology is seldom considered except as a prelude to, or indication of, cell death. However, evidence from diverse fields strongly implicates membrane disruption as a key precipitating event in the pathological responses to various stimuli. Dynamic mechanical loading of neural cells produces an acute disruption of the plasma membrane as indicated by a rapid and transient release of LDH from the cytoplasm of injured cells. In this report, we show that this cellular level injury is not immediately fatal, but rather gives rise to a cascade of signaling events that lead to cell death in the long term. In our model, over 50% of the cells were dead at 24 hours post injury, the majority of which were apoptotic as assessed by the TUNEL assay using flow cytometry. Though many of the signaling pathways involved in this response to injury have been studied, the link between the initial membrane damage and the subsequent signaling is poorly understood. We report for the first time that treating injured neurons with an agent that promotes resealing of membrane pores can rescue the cells from both necrotic cell death and apoptosis at 24 hours post injury. Treatment with the nonionic surfactant, poloxamer 188 (P188), at 15 minutes post injury restored cell viability at 24 hours to control values. The role of the pro-apoptosis MAP kinase, p38, in cell death following injury was investigated using Western blot analysis. Activation of p38 was increased over 2-fold at 15 minutes post injury. P188 treatment at 10 minutes inhibited p38 activation. However, treatment with a specific inhibitor of p38 activation produced only a partial reduction in apoptosis and had no effect on necrotic cell death. These data suggest multiple signaling pathways are involved in the long term response of neurons to mechanical injury. Furthermore, the putative mechanism of action of P188 to promote membrane resealing suggests that the acute membrane damage due to trauma is a critical precipitating event lying upstream of the many signaling cascades that contribute to the subsequent pathology.

scholarly journals The Lipid-Chaperon Hypothesis: A Common Molecular Mechanism of Membrane Disruption by Intrinsically Disordered Proteins

2020 ◽  
Author(s):  
Michele F. M. Sciacca ◽  
Fabio Lolicato ◽  
Carmelo Tempra ◽  
Federica Scollo ◽  
Bikash R. Sahoo ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Membrane Damage ◽  
Amyloid Β ◽  
Disordered Proteins ◽  
Amyloid Formation ◽  
Intrinsically Disordered ◽  
Molecular Events ◽  
Membrane Poration ◽  
Synuclein Proteins

<p>Increasing number of human diseases have been shown to be linked to aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, and α-synuclein are, indeed, involved in type-II diabetes, Alzheimer’s, and Parkinson’s, respectively. Despite the correlation of the toxicity of these proteins at early aggregation stages with membrane damage, the molecular events underlying the process is quite complex to understand. In this study, we demonstrate the crucial role of free lipids in the formation of lipid-protein complex, which enables an easy membrane insertion for amylin, amyloid-β, and α-synuclein. Experimental results from a variety of biophysical methods and molecular dynamics results reveal this common molecular pathway in membrane poration is shared by amyloidogenic (amylin, amyloid-β, and α-synuclein) and non-amyloidogenic (rat IAPP, β-synuclein) proteins. Based on these results, we propose a “lipid-chaperone” hypothesis as a unifying framework for protein-membrane poration.<b></b></p>

Role of spectrin in membrane fusion and in shape change of human erythrocyte ghost

1978 ◽  
Vol 36 (2) ◽  
pp. 328-329
Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston
Keyword(s):  
Conformational Changes ◽  
Human Erythrocyte ◽  
Shape Change ◽  
Membrane Surface ◽  
Slight Modification ◽  
Active Role ◽  
Main Role ◽  
Bank Blood ◽  
Human Erythrocyte Ghost

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.

Elucidation of block boundaries as the dissolution channels in hydrated cement

1978 ◽  
Vol 36 (1) ◽  
pp. 484-485
Author(s):  
N.V. Belov ◽  
U.I. Papiashwili ◽  
B.E. Yudovich
Keyword(s):  
Liquid Phase ◽  
Grain Boundaries ◽  
Benzoyl Peroxide ◽  
Phase Contrast ◽  
Active Role ◽  
Point Of View ◽  
Hardened Cement ◽  
Hydrated Cement ◽  
Hardened Cement Paste

It has been almost universally adopted that dissolution of solids proceeds with development of uniform, continuous frontiers of reaction.However this point of view is doubtful / 1 /. E.g. we have proved the active role of the block (grain) boundaries in the main phases of cement, these boundaries being the areas of hydrate phases' nucleation / 2 /. It has brought to the supposition that the dissolution frontier of cement particles in water is discrete. It seems also probable that the dissolution proceeds through the channels, which serve both for the liquid phase movement and for the drainage of the incongruant solution products. These channels can be appeared along the block boundaries.In order to demonsrate it, we have offered the method of phase-contrast impregnation of the hardened cement paste with the solution of methyl metacrylahe and benzoyl peroxide. The viscosity of this solution is equal to that of water.

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