Mammalian Sulfur Amino Acid Metabolism: A Nexus Between Redox Regulation, Nutrition, Epigenetics, and Detoxification

Pajares, Marı́a A.

doi:10.1089/ars.2017.7237

Cited by 29 publications

(39 citation statements)

References 424 publications

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“…The alterations in chaperone levels, in addition to the impairment in some amino acid's metabolism, such as proline, previously mentioned, and sulfur amino acids [46], due to the low levels of AHCY found in OC cells, could be also indicative of alteration of protein quality. Moreover, impairment in transsulfuration pathways may have consequences in epigenetic modulation of gene expression, glutathione, and taurine synthesis, as well as in proteoglycan sulfation, which is crucial for cartilage and bone homeostasis, and remodeling [47][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Proteome Alterations in Equine Osteochondrotic Chondrocytes

Chiaradia

Pepe

Orvietani

et al. 2019

IJMS

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Osteochondrosis is a failure of the endochondral ossification that affects developing joints in humans and several animal species. It is a localized idiopathic joint disorder characterized by focal chondronecrosis and growing cartilage retention, which can lead to the formation of fissures, subchondral bone cysts, or intra-articular fragments. Osteochondrosis is a complex multifactorial disease associated with extracellular matrix alterations and failure in chondrocyte differentiation, mainly due to genetic, biochemical, and nutritional factors, as well as traumas. This study describes the main proteomic alterations occurring in chondrocytes isolated from osteochondrotic cartilage fragments. A comparative analysis performed on equine osteochondrotic and healthy chondrocytes showed 26 protein species as differentially represented. In particular, quantitative changes in the extracellular matrix, cytoskeletal and chaperone proteins, and in cell adhesion and signaling molecules were observed in osteochondrotic cells, compared to healthy controls. Functional group analysis annotated most of these proteins in “growth plate and cartilage development”, while others were included in “glycolysis and gluconeogenesis”, “positive regulation of protein import”, “cell–cell adhesion mediator activity”, and “mitochondrion nucleoid”. These results may help to clarify some chondrocyte functional alterations that may play a significant role in determining the onset and progression of equine osteochondrosis and, being related, of human juvenile osteochondrosis.

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Section: Discussionmentioning

confidence: 99%

Proteome Alterations in Equine Osteochondrotic Chondrocytes

Chiaradia

Pepe

Orvietani

et al. 2019

IJMS

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“…From its side, cysteine can be synthesized within the cell from methionine via transsulfuration pathway 29 . However, previous studies showed that this does not meet the requirements of highly proliferative and/or oxidatively compromised cells (such as cancer cells), which thus, largely rely on the import of this amino acid from the extracellular space 30 . Accordingly, the major transporter for the oxidized form (dominant form in the serum and almost exclusive form in the culture media) of CySH (cystine, CySSCy), known as Xc- system, seems to be consistently up-regulated within different types of cancer 31 – 40 .…”

Section: Ferroptosis—in the Perspectivementioning

confidence: 96%

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

et al. 2020

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Contextualisation of the new type of cell death called “ferroptosis” opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which “ferroptosis inducers” can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.

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“…In the liver, a particular metabolic pathway called transsulfuration permits the supply of cysteine by conversion of an essential amino acid: methionine. Yet, this amino acid interconversion is insufficient to provide the cysteine requirements of rapidly dividing cancer cells (4). As mentioned previously, cysteine is a thiol-containing amino acid, which nucleophilicity makes it highly susceptible to redox changes.…”

Section: Cysteine a Key Player In Tumor Metabolismmentioning

confidence: 99%

Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death

2020

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Cancer cells are characterized as highly proliferative at the expense of enhancement of metabolic rate. Consequently, cancer cells rely on antioxidant defenses to overcome the associated increased production of reactive oxygen species (ROS). The reliance of tumor metabolism on amino acids, especially amino acid transport systems, has been extensively studied over the past decade. Although cysteine is the least abundant amino acid in the cell, evidences described it as one of the most important amino acid for cell survival and growth. Regarding its multi-functionality as a nutrient, protein folding, and major component for redox balance due to its involvement in glutathione synthesis, disruption of cysteine homeostasis appears to be promising strategy for induction of cancer cell death. Ten years ago, ferroptosis, a new form of non-apoptotic cell death, has been described as a result of cysteine insufficiency leading to a collapse of intracellular glutathione level. In the present review, we summarized the metabolic networks involving the amino acid cysteine in cancer and ferroptosis and we focused on describing the recently discovered glutathione-independent pathway, a potential player in cancer ferroptosis resistance. Then, we discuss the implication of cysteine as key player in ferroptosis as a precursor for glutathione first, but also as metabolic precursor in glutathione-independent ferroptosis axis.

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Mammalian Sulfur Amino Acid Metabolism: A Nexus Between Redox Regulation, Nutrition, Epigenetics, and Detoxification

Cited by 29 publications

References 424 publications

Proteome Alterations in Equine Osteochondrotic Chondrocytes

Proteome Alterations in Equine Osteochondrotic Chondrocytes

Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis

Cysteine Depletion, a Key Action to Challenge Cancer Cells to Ferroptotic Cell Death

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