Glycosyl chains and 25‐hydroxycholesterol contribute to the intracellular transport of amyloid beta (Aβ‐42) in Jurkat T cells

Sharma, Neha; Baek, Keang O K; Phan, Huong T.T.; Shimokawa, Naofumi; Takagi, Masahiro

doi:10.1002/2211-5463.12234

Cited by 13 publications

(9 citation statements)

References 56 publications

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“…On the other hand, Jurkat cell line, which is a parent cell line of 2D3 cell line, is stable to viability and can respond to TCR signals. Jurkat cells can form lipid raft [ 38 ], like primary human T cells, and increase CD3 ζ and ERK phosphorylation through cholesterol removal [ 39 ]. Therefore, it appears that Jurkat cells functionally mimic primary human T cells, and thus 2D3 cell line should be useful for the study of how TCR avidity controls T cell responses and their fate.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity

et al. 2018

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Adoptive T-cell therapy with T cell receptor (TCR) -engineered T cells is an attractive strategy for cancer treatment and the success in this therapy is dependent on the functional avidity of the transduced TCRs against targeted tumor antigens. Therefore, the establishment of the methodology of the efficient and precise evaluation of TCR functional avidity has been awaited. Here, we show a novel platform cell line, named 2D3, which enables the functional avidity of transduced TCRs to be evaluated efficiently and precisely. In the 2D3, the precise TCR functional avidity of transduced TCRs is easily evaluable by the expression of green fluorescent protein (GFP) reporter gene driven by nuclear factor of activated T cells (NFAT) activation via TCR signaling. Four different TCRs of HLA-A*24:02-restricted Wilms’ tumor gene 1 (WT1)-specific CD8+ cytotoxic T lymphocytes (CTLs) were transduced into 2D3 cells and the functional avidities of these four TCRs were evaluated. The evaluated functional avidity of these TCRs positively correlated with cell proliferation, cytokine production, and WT1-specific cytotoxicity of the TCR-transduced CD8+ T cells in response to WT1 antigen. These results showed that 2D3 cell line was a novel and stable tool useful for the efficient and precise evaluation of the functional avidity of isolated and transduced TCRs in developing TCR-based immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity

et al. 2018

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“…The accelerated progression of AD may be influenced by persistent hypercholesterolemia, with elevated levels of 27-hydroxycholesterol (27-OHC) in the brain and circulation, affecting metabolism and cholesterol regulation [12]. Lipoprotein (a), which is associated with pro-inflammatory oxidized phospholipids, is another player.…”

Section: Cholesterol Oxidation Productsmentioning

confidence: 99%

Metabolism and the Effect of Animal-Derived Oxysterols in the Diet on the Development of Alzheimer’s Disease

Choroszyński¹,

Barcikowska²,

Barczak

2022

Ann Nutr Metab

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Background: The rapid worldwide increase in the incidence of Alzheimer’s disease is associated with changing nutrition patterns. Recently, some articles have highlighted the link between Alzheimer’s disease and dietary cholesterol. It was found that elevated levels of some of its fractions in the brain and circulation affect metabolism. Summary: Previous studies have considered the relationship between Alzheimer’s disease and oxidized cholesterol molecules in the brain. To date, there are limited data available on the relationship between oxidized cholesterol in the brain and Alzheimer’s disease. There is a link between a diet high in cholesterol and its oxidized forms, leading to hypercholesterolemia, which is one of significant risk factors of dementia, and Alzheimer’s disease. Oxidized cholesterol can be absorbed in the small intestine and cross the blood-brain barrier, leading to increased inflammation and endogenous oxidative process. Animal-origin foods are sources of oxidized cholesterol, with cholesterol oxidation beginning already after slaughter and occurring during storage and processing. Key Messages: High-heat food preparation and storage of cooked products in the refrigerator followed by subsequent heating may significantly increase the amount of oxidized cholesterol products. Therefore, a diet low in cholesterol oxidation products and high in plants with antioxidative properties seems to be most preventable and should be implemented as early as possible.

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“…Some of these aspects have recently been elucidated: in Jurkat T cells, 25‐HC appears to alter membrane properties, facilitating the internalization and intracellular transport of protofibrillar Aβ 42, which ultimately leads to apoptosis by inducing endoplasmic reticulum stress . Membrane remodeling, as well as Aβ production driven by activation of β‐secretase‐1, have also been reported in SH‐SY5Y neuronal‐like cells exposed to 27‐HC …”

Section: Oxysterols As Pathological Bioactive Compounds: a Possible Lmentioning

confidence: 99%

Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

Sottero

Leonarduzzi

Testa

et al. 2018

Euro J Lipid Sci & Tech

102

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Non‐enzymatic and enzymatic oxidation of lipids has long been a primary issue in human pathophysiology, with special emphasis on diet‐ and nutrition‐related aspects. While there is no doubt that the n‐3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid, and docosahexaenoic acid, exert anti‐inflammatory, inflammation resolving, and immunomodulatory effects in different model systems, their non‐enzymatic oxidation during food storage and cooking, as well as during gastrointestinal digestion, can give rise to excessive amounts of quite reactive aldehydic end‐products, in particular 4‐hydroxyhexenal. However, the non‐enzymatic oxidation of n‐6 PUFAs is, in principle, far more harmful, not least because one of its main end‐products, 4‐hydroxynonenal, has been shown to be associated with the progression of a number of human diseases. Several cholesterol oxidation products, known as oxysterols, are also of primary nutritional importance; these can be generated in the human body through both enzymatic and non‐enzymatic reactions, but may also be present in the diet in excessive amounts due to the autoxidation of cholesterol‐containing foods. Their potential contribution to the pathogenesis and progression of human diseases in which hypercholesterolemia is a primary risk factor, such as atheroclerosis, Alzheimer's disease, and some forms of cancers, has been unanimously recognized. Practical Applications: This review highlights the importance of certain lipid oxidation products, namely 4‐hydroxyalkenals and oxysterols, in the modulation of processes fundamental to human health and disease. The observations and facts reviewed here underline the need to carefully consider the pros and cons of the dietary intake and metabolic fate of n‐3 PUFA, n‐6 PUFA, and cholesterol, when producing, storing, and processing lipid‐containing food. Lipid oxidation is a common process that occurs through both enzymatic and non‐enzymatic reactions. It is responsible for the formation of several compounds, including polyunsaturated fatty acid (PUFA)‐derived 4‐hydroxyalkenals and cholesterol oxidation products, namely oxysterols. Depending on their concentrations, these molecules possess physiopathological properties involved in cell viability and function. At high concentrations, such as those resulting from intense oxidative stress or excessive fatty food intake, they are associated to the onset of many diseases. A correct diet regimen, improved food processing and storage, and suitable antioxidant supplementation, should be implemented to counteract promotion of disease development by excess oxidized lipids. (HHE, 4‐hydroxyhexenal; HNE, 4‐hydroxynonenal; ROS, reactive oxygen species).

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Glycosyl chains and 25‐hydroxycholesterol contribute to the intracellular transport of amyloid beta (Aβ‐42) in Jurkat T cells

Cited by 13 publications

References 56 publications

Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity

Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity

Metabolism and the Effect of Animal-Derived Oxysterols in the Diet on the Development of Alzheimer’s Disease

Lipid Oxidation Derived Aldehydes and Oxysterols Between Health and Disease

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