Redox Signaling by Reactive Electrophiles and Oxidants

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(18), P. 8798 - 8888

Published: Aug. 27, 2018

The concept of cell signaling in the context nonenzyme-assisted protein modifications by reactive electrophilic and oxidative species, broadly known as redox signaling, is a uniquely complex topic that has been approached from numerous different multidisciplinary angles. Our Review reflects on five aspects critical for understanding how nature harnesses these noncanonical post-translational to coordinate distinct cellular activities: (1) specific players their generation, (2) physicochemical properties, (3) mechanisms action, (4) methods interrogation, (5) functional roles health disease. Emphasis primarily placed latest progress field, but several classical work likely forgotten/lost are also recollected. For researchers with interests getting into our anticipated function primer. expert, we aim stimulate thought discussion about fundamentals nuances specificity/selectivity timing this sophisticated yet fascinating arena at crossroads chemistry biology.

Language: Английский

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Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship

Cancer Letters, Journal Year: 2017, Volume and Issue: 413, P. 102 - 109

Published: Oct. 27, 2017

In order to adapt the reduced availability of nutrients and oxygen in tumor microenvironment increased requirements energy building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result an production lactate, nitric oxide, reactive species, prostaglandins other byproducts arachidonic acid metabolism influence both composition inflammatory function tumor-associated macrophages (TAMs). response cues present TME, among which products altered cell metabolism, TAMs are also required reprogram with activation glycolysis, fatty synthesis nitrogen cycle metabolism. These functional reprogramming includes cytokines angiogenetic factors, contribute progression metastasis. Understanding governing intricate relationship between represents essential step towards developing novel therapeutic approaches targeting immune potentiate tumoricidal potential circumvent therapy resistance.

Language: Английский

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Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Jan. 16, 2018

Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance LD in colorectal cancer (CRC) biology incompletely understood under chemotherapeutic conditions. Since drug resistance major obstacle to treatment success, we sought determine contribution chemotherapy CRC. Here show that content CRC cells positively correlates with expression lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme supporting phosphatidylcholine synthesis. We also demonstrate drives cell-death 5-fluorouracil and oxaliplatin treatments both vitro vivo. Mechanistically, impairs caspase cascade activation ER stress responses. Notably, associated reduction immunogenic cell death CD8+ T infiltration mouse tumour grafts metastatic tumours patients. Collectively our findings highlight LPCAT2-mediated as druggable mechanism restore sensitivity.

Language: Английский

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Tumor microenvironment targeted nanotherapeutics for cancer therapy and diagnosis: A review

Acta Biomaterialia, Journal Year: 2019, Volume and Issue: 101, P. 43 - 68

Published: Sept. 10, 2019

Language: Английский

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Lipid metabolism in sickness and in health: Emerging regulators of lipotoxicity

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(18), P. 3708 - 3730

Published: Sept. 1, 2021

Language: Английский

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