Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)

Pompella, Alfonso; Corti, Alessandro; Visvikis, Athanase

doi:10.3389/fonc.2022.920316

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…Decreased levels of reduced GSH and enzymes involved in GSH synthesis were identified to play a key role in cisplatin resistance [157]. Pompella et al showed that the enzyme gamma-glutamyltransferase 1 (GGT1) expression on the surface of the cell favors the cellular resupply of antioxidant glutathione (GSH) which in turn favors protection against cisplatin by the formation of glycyl-cysteine dipeptide which forms an adduct with cisplatin thereby preventing its entry into the cell and its interaction with the DNA [158,159]. Platinum-resistant ovarian cancer cells showed increased dependency on glutamine metabolism as ASCT2 and GA were significantly upregulated.…”

Section: Amino Acid Metabolismmentioning

confidence: 99%

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

et al. 2023

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Ovarian cancers are tumors that originate from the different cells of the ovary and account for almost 4% of all the cancers in women globally. More than 30 types of tumors have been identified based on the cellular origins. Epithelial ovarian cancer (EOC) is the most common and lethal type of ovarian cancer which can be further divided into high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. Ovarian carcinogenesis has been long attributed to endometriosis which is a chronic inflammation of the reproductive tract leading to progressive accumulation of mutations. Due to the advent of multi-omics datasets, the consequences of somatic mutations and their role in altered tumor metabolism has been well elucidated. Several oncogenes and tumor suppressor genes have been implicated in the progression of ovarian cancer. In this review, we highlight the genetic alterations undergone by the key oncogenes and tumor suppressor genes responsible for the development of ovarian cancer. We also summarize the role of these oncogenes and tumor suppressor genes and their association with a deregulated network of fatty acid, glycolysis, tricarboxylic acid and amino acid metabolism in ovarian cancers. Identification of genomic and metabolic circuits will be useful in clinical stratification of patients with complex etiologies and in identifying drug targets for personalized therapies against cancer.

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Section: Amino Acid Metabolismmentioning

confidence: 99%

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

et al. 2023

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“…Mutations in Slc7a11, Ggt1, Mfsd12, Clcn7, Ostm1, Sox10, and several as yet undefined genes have all been shown to reduce pheomelanin pigmentation in mouse with no or modest impact on eumelanin production [10,[66][67][68][69][70][71][72]. Several of these genes (Slc7a11, Mfsd12, and Ggt1) impact cysteine uptake, intracellular transport, or incorporation into glutathione [10,73,74], and thus might share a mechanistic basis with Comtd1 for their impact on pheomelanin synthesis. Clcn7 and Ostm1 encode the subunits of the CLC7 chloride transporter that impacts lysosomal pH [75], and thus might alter the pH of melanosomes promoting specifically pheomelanin synthesis.…”

Section: Plos Geneticsmentioning

confidence: 99%

A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken

Tranell

Harper

et al. 2023

PLoS Genet

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The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5th exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin.

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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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Redox Mechanisms in Cisplatin Resistance of Cancer Cells: The Twofold Role of Gamma-Glutamyltransferase 1 (GGT1)

Cited by 5 publications

References 17 publications

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence

A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken

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

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