Release of trivalent chromium from serum transferrin is sufficiently rapid to be physiologically relevant

Edwards, Kyle; Kim, Hannah; Vincent, John B.

doi:10.1016/j.jinorgbio.2019.110901

Cited by 20 publications

(11 citation statements)

References 30 publications

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“…Vanadium(IV) and chromium(III) (Cr(III)) have long been studied for their insulin-enhancing properties. While their essentiality in humans is debated, they exhibit tremendous therapeutic potential as anti-type 2 diabetic agents [85][86][87][88][89][90][91][92]. Both manifest their insulin-enhancing effect via related but distinct molecular mechanistic routes that are believed to be tied to the transport offered by sTf.…”

Section: Stf As a Vehicle For The Anti-type 2 Diabetes V(iv) And Cr(iii)mentioning

confidence: 99%

“…Cr(III) absorbed from dietary sources into the body becomes 80% sTf bound [114]. It is believed to bind in the canonical modality at the metal binding site [13,91,92]. Very recently, a crystal structure for Cr(III)-bound sTf was obtained, which shows Cr(III) coordinated at the C-site, in closed-conformation, canonical modality with malonate substituting for carbonate [115].…”

Section: The Anti-type 2 Diabetes Mechanism Of Action Of Cr(iii)mentioning

confidence: 99%

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Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

et al. 2020

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Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

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Section: Stf As a Vehicle For The Anti-type 2 Diabetes V(iv) And Cr(iii)mentioning

confidence: 99%

Section: The Anti-type 2 Diabetes Mechanism Of Action Of Cr(iii)mentioning

confidence: 99%

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

et al. 2020

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“…A very compelling finding is that the presence of the TfR further accelerates Cr(III) release from sTf. The metal ion should be fully released from the Cr2-sTf-TfR complex within 15 minutes, making it fast enough for physiological transport of Cr(III) [92]. The finding of Cr(III) retention by sTf-TfR by Lay et al might be an artifact of insufficient time allowed to observe metal release and not using physiologically relevant anions in their bio-layer interferometry approach [64].…”

Section: The Anti-type 2 Diabetes Mechanism Of Action Of Cr(iii)mentioning

confidence: 99%

Section: Stf As a Vehicle For The Anti-type 2 Diabetes V(iv) And Cr(iii)mentioning

confidence: 99%

“…Cr(III) absorbed from dietary sources into the body becomes ~80% sTf bound [114]. It is believed to bind in the canonical modality at the metal binding site [12,91,92]. In 1986, Yamamoto et al discovered chromodulin, a Cr-binding oligopeptide present inside the cytoplasm and nucleus in its apo form [115].…”

Section: The Anti-type 2 Diabetes Mechanism Of Action Of Cr(iii)mentioning

confidence: 99%

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Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Benjamín-Rivera¹,

Cardona-Rivera²,

Vázquez-Maldonado³

et al. 2020

Preprint

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Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

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Mechanisms and individuality in chromium toxicity in humans

Pavesi

Moreira

2020

J of Applied Toxicology

170

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With regards to health, chromium (Cr) is an ambiguous chemical element. Although it is considered to be an important micronutrient, it also is connected with several pathologies, including carcinogenicity. The mechanism of action of Cr and its compounds in humans is not yet fully understood. Currently, three possible mechanisms have been proposed for carcinogenesis: Cr(VI)‐induced multistage carcinogenesis, genomic instability, and epigenetic modification. Therefore, in addition to the toxicity of this metal and its ions, human susceptibility to Cr‐induced pathologies depends on external factors and individual characteristics, such as enzymatic polymorphisms, carriers, endogenous reducing system, adduct formation and stability, and efficiency of DNA repair mechanisms, among other factors. In fact, the variability of individual molecular constitutive factors, such as individual polymorphisms, creates an individualized environment for Cr toxicity. This mini‐review contemplates the essential variables in this process.

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Release of trivalent chromium from serum transferrin is sufficiently rapid to be physiologically relevant

Cited by 20 publications

References 30 publications

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Mechanisms and individuality in chromium toxicity in humans

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