Cystine/glutamate antiporter xCT controls skeletal muscle glutathione redox, bioenergetics and differentiation

Kanaan, Michel N.; Pileggi, Chantal A.; Karam, Charbel Y.; Kennedy, Luke S.; Fong-McMaster, Claire; Cuperlovic-Culf, Miroslava; Harper, Mary-Ellen

doi:10.1016/j.redox.2024.103213

Cited by 2 publications

References 95 publications

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Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols

Niu,

Dong,

Niu

2024

Phytotherapy Research

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Oxidative stress is recognized to have a central role in the initiation and progression of Parkinson's disease (PD). Within the brain, neurons are particularly sensitive to oxidation due in part to their weak intrinsic antioxidant defense. Theoretically, neurons mostly depend on neighboring astrocytes to provide antioxidant protection by supplying cysteine‐containing products for glutathione (GSH) synthesis. Astrocytes and neurons possess several amino acid transport systems for GSH and its precursors. Indeed, GSH is the most abundant intrinsic antioxidant in the central nervous system. The GSH depletion and/or alterations in its metabolism in the brain contribute to the pathogenesis of PD. Noteworthy, polyphenols possess potent antioxidant activity and can augment the GSH redox system. Numerous in vitro and in vivo studies have indicated that polyphenols exhibit potent neuroprotective effects in PD. Epidemiological studies have found an association between the consumption of dietary polyphenols and a lower PD risk. In this review, we summarize current knowledge on the biosynthesis and metabolism of GSH in the brain, with an emphasis on their contribution and therapeutic potential in PD. In particular, we focus on polyphenols that can increase brain GSH levels against PD. Furthermore, some current challenges and future perspectives for polyphenol‐based therapies are also discussed.

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Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols

Niu,

Dong,

Niu

2024

Phytotherapy Research

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A Novel Nanomedicine for Osteosarcoma Treatment: Triggering Ferroptosis through GSH Depletion and Inhibition for Enhanced Synergistic PDT/PTT Therapy

Xu,

Ma,

Zhang

et al. 2024

Preprint

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Osteosarcoma treatment remains challenging due to the limitations of single-modality therapies.To address this, we designed a carrier-free nanomedicine SRF@CuSO4.5H2O@IR780 (CSIR) for synergistic ferroptosis, photodynamic therapy (PDT), and photothermal therapy (PTT) in osteosarcoma. Interestingly, CSIR could harness the enhanced permeability and retention (EPR) effect to effectively enter tumors. Copper ions (Cu2+) within CSIR could react with the reductive intracellular environment, depleting glutathione (GSH) levels. Near-infrared (NIR) irradiation of CSIR further depleted GSH through reactive oxygen species (ROS) generation. Additionally, CSIR released sorafenib (SRF), which inhibited cystine-glutamate antiporter system xCT (xCT), thereby blocking GSH biosynthesis. RNA sequencing data confirmed ferroptosis induction by CSIR. This synergistic strategy of GSH depletion-induced ferroptosis, enhanced PDT, and photothermal cascade holds promise for improved osteosarcoma treatment and future nanomedicine design.

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Cystine/glutamate antiporter xCT controls skeletal muscle glutathione redox, bioenergetics and differentiation

Cited by 2 publications

References 95 publications

Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols

Role of Glutathione in Parkinson's Disease Pathophysiology and Therapeutic Potential of Polyphenols

A Novel Nanomedicine for Osteosarcoma Treatment: Triggering Ferroptosis through GSH Depletion and Inhibition for Enhanced Synergistic PDT/PTT Therapy

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