Amyloid toxicity and platelet‐activating factor signaling

Sirangelo, Ivana; Irace, Gaetano; Balestrieri, Maria Luisa

doi:10.1002/jcp.24284

Cited by 5 publications

(4 citation statements)

References 122 publications

(147 reference statements)

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“…Cytotoxicity of the amyloid oligomeric aggregates mostly depends on their ability to interact with the cell membrane and form annular pores altering membrane permeability. Impaired membrane permeability leads to cell homeostasis imbalance and cell dysfunction (Sirangelo et al, 2009;Stefani, 2012;Cecchi and Stefani, 2013;Vilasi et al, 2013;Sirangelo et al, 2013Sirangelo et al, , 2014. The cytotoxicity induced by glycated apomyoglobin could involve the activation of different signalling pathways; in fact, in addition to directly affecting protein structure and function, AGEs also exert cellular effects mediated by specific AGEs receptors (RAGE) (Vlassara et al, 1995;Stern et al, 2002;Chen et al, 2010;Yan et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Glycation of Wild‐Type Apomyoglobin Induces Formation of Highly Cytotoxic Oligomeric Species

Iannuzzi

Carafa

Altucci

et al. 2015

Journal Cellular Physiology

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Protein glycation is a non-enzymatic, irreversible modification of protein amino groups by reactive carbonyl species leading to the formation of advanced glycation end products (AGEs). Several proteins implicated in neurodegenerative diseases have been found to be glycated in vivo and the extent of glycation is related to the pathologies of the patients. Although it is now accepted that there is a direct correlation between AGEs formation and the development of neurodegenerative diseases related to protein misfolding and amyloid aggregation, several questions still remain unanswered: whether glycation is the triggering event or just an additional factor acting on the aggregation pathway. We have recently shown that glycation of the amyloidogenic W7FW14F apomyoglobin mutant significantly accelerates the amyloid fibrils formation providing evidence that glycation actively participates to the process. In the present study, to test if glycation can be considered also a triggering factor in amyloidosis, we evaluated the ability of different glycation agents to induce amyloid aggregation in the soluble wild-type apomyoglobin. Our results show that glycation covalently modifies apomyoglobin and induces conformational changes that lead to the formation of oligomeric species that are not implicated in amyloid aggregation. Thus, AGEs formation does not trigger amyloid aggregation in the wild-type apomyoglobin but only induce the formation of soluble oligomeric species able to affect cell viability. The molecular bases of cell toxicity induced by AGEs formed upon glycation of wild-type apomyoglobin have been also investigated.

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Section: Discussionmentioning

confidence: 99%

Glycation of Wild‐Type Apomyoglobin Induces Formation of Highly Cytotoxic Oligomeric Species

Iannuzzi

Carafa

Altucci

et al. 2015

Journal Cellular Physiology

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“…The previous demonstration that PAF takes part to the mechanisms involved in Aβ‐amyloid toxicity led to unravel the mechanisms involved in the regulation of the levels of this inflammatory lipid mediator in the nervous system [Goracci et al, ; Shi et al, ; Sirangelo et al, ]. Indeed, the activation of the enzymes of the PAF biosynthetic route, responsible for the increased levels of PAF under pathological conditions, represents a possible pharmacologic target [Bate et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…The PAF-induced neuronal toxicity is mainly characterized by increased levels of PAF due to the upregulation of its biosynthesis or downregulation of its degradation [Goracci et al, 2009]. An increased PAF production in the brain, due to the activation of the phospholipase A 2 by Ab peptides, has been implicated in Alzheimer disease [Bate et al, 2004a;Kriem et al, 2005;Farooqui and Horrocks, 2006;Bate et al, 2008;Sanchez-Mejia et al, 2008;Sirangelo et al, 2013]. High concentrations of PAF were shown to be able to reproduce many of the effects of Ab peptides on neurons [Bate et al, 2006[Bate et al, , 2008.…”

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confidence: 99%

Platelet‐Activating Factor Mediates the Cytotoxicity Induced by W7FW14F Apomyoglobin Amyloid Aggregates in Neuroblastoma Cells

Sirangelo

Giovane

Maritato

et al. 2014

J of Cellular Biochemistry

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W7FW14F apomyoglobin (W7FW14F ApoMb) amyloid aggregates induce cytotoxicity in SH-SY5Y human neuroblastoma cells through a mechanism not fully elucidated. Amyloid neurotoxicity process involves calcium dyshomeostasis and reactive oxygen species (ROS) production. Another key mediator of the amyloid neurotoxicity is Platelet-Activating Factor (PAF), an inflammatory phospholipid implicated in neurodegenerative diseases. Here, with the aim at evaluating the possible involvement of PAF signaling in the W7FW14F ApoMb-induced cytotoxicity, we show that the presence of CV3899, a PAF receptor (PAF-R) antagonist, prevented the detrimental effect of W7FW14F ApoMb aggregates on SH-SY5Y cell viability. Noticeably, we found that the activation of PAF signaling, following treatment with W7FW14F ApoMb, involves a decreased expression of the PAF acetylhydroase II (PAF-AH II). Interestingly, the reduced PAF-AH II expression was associated with a decreased acetylhydrolase (AH) activity and to an increased sphingosine-transacetylase activity (TA(S)) with production of N-acetylsphingosine (C2-ceramide), a well known mediator of neuronal caspase-dependent apoptosis. These findings suggest that an altered PAF catabolism takes part to the molecular events leading to W7FW14F ApoMb amyloid aggregates-induced cell death.

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“…Emerging evidence implies that neuromelanin is cytoprotective when contained within neuronal cells but causes cytotoxic effect when released by damaged neuron cells . Taken together, the melanosomal amyloid toxicity may be summarized into several aspects: (i) Amyloid changes the structure of the melanosomes and leads to leaking of the melanosomal contents including amyloid itself, melanin and melanin intermediates; (ii) Amyloid interaction with ROS and RNS augments the detelerious effect of these species; (iii) Amyloid may disrupt the cellular membrane leading to altered signal transduction, as has been proposed in other cell types . …”

Section: The Amyloid–melanin Connectionmentioning

confidence: 99%

Amyloids, melanins and oxidative stress in melanomagenesis

Liu‐Smith

Poe

Farmer

et al. 2014

Experimental Dermatology

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Melanoma has traditionally been viewed as an ultra-violet (UV) radiation induced malignancy. While UV is a common inducing factor, other endogenous stresses such as metal ion accumulation or the melanin pigment itself, may provide alternative pathways to melanoma progression. Eumelanosomes within melanoma often exhibit disrupted membranes and fragmented pigment which may be due to alterations in their amyloid-based striatial matrix. The melanosomal amyloid can itself be toxic, especially in combination with reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by endogenous NADPH oxidase (NOX) and nitric oxide synthase (NOS) enzymes; a toxic mix that may initiate melanomagenesis. Further understanding of the loss of the melanosomal organization, the behavior of the exposed melanin, and the induction of ROS/RNS in melanomas may provide critical insights into this deadly disease.

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Amyloid toxicity and platelet‐activating factor signaling

Cited by 5 publications

References 122 publications

Glycation of Wild‐Type Apomyoglobin Induces Formation of Highly Cytotoxic Oligomeric Species

Glycation of Wild‐Type Apomyoglobin Induces Formation of Highly Cytotoxic Oligomeric Species

Platelet‐Activating Factor Mediates the Cytotoxicity Induced by W7FW14F Apomyoglobin Amyloid Aggregates in Neuroblastoma Cells

Amyloids, melanins and oxidative stress in melanomagenesis

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