Evaluation of divalent metal transporter 1 (DMT1) (rs224589) polymorphism on blood lead levels of occupationally exposed individuals

Mani, Monica Shirley; Dsouza, Venzil Lavie; Dsouza, Herman Sunil

doi:10.1016/j.toxlet.2021.10.002

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…This could possibly be due to his slowed colonic transit time due to a possible lack of fiber in diet as well as his iron deficiency, leading to increased absorption through divalent metal transporter 1 (DMT1). DMT1 is a transmembrane protein and a major iron transporter essential in iron absorption [9]. It is expressed in many tissues of the body, particularly in the small intestine, erythroid cells, lungs, liver, kidneys, and brain [10].…”

Section: Discussionmentioning

confidence: 99%

“…Lead shares similar divalent cationic properties with iron, thus resulting in lead behaving as an analogue to iron. This, in turn, leads to altered metabolism of iron and intracellular iron homeostasis [9]. In the setting of iron deficiency, it has been noted that DMT1 increases its absorption and this manifests as lead toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…In the setting of iron deficiency, it has been noted that DMT1 increases its absorption and this manifests as lead toxicity. Furthermore, DMT1 exhibits effects of molecular mimicry, as evidenced by inhibition of lead absorption in the presence of iron supplementation in yeast and human fibroblast cells [9].…”

Section: Discussionmentioning

confidence: 99%

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Asymptomatic Lead Poisoning in a Pediatric Patient

Senanayake¹,

Rahman²,

Safwat³

et al. 2023

Cureus

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Lead poisoning is a harmful condition, potentially resulting in irreversible impairments in neurocognition and behavioral development in the pediatric population. Rarely, life-threatening complications may ensue. We report a case of an asymptomatic four-year-old patient presenting with elevated lead levels (74.7 µg/dL) detected on routine blood lead screening at a well-child examination. The patient has a history significant for atopic disease, namely atopic dermatitis, seasonal allergic rhinitis, and food allergies. Overall, the asymptomatic nature of lead poisoning warrants judicious screening in the pediatric population due to the potential for neurologic complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Asymptomatic Lead Poisoning in a Pediatric Patient

Senanayake¹,

Rahman²,

Safwat³

et al. 2023

Cureus

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“…19,20 Moreover, divalent metal transporter 1 (DMT1) is expressed in duodenal crypt cells and is also involved in transporting several metal ions into intestinal epithelial cells. 21 There are four distinct metallothionein (MT) isoforms, among which MT1 is found in all organs and is responsible for transporting zinc from the apical membrane to the basement membrane within small intestine epithelial cells. 22 The main transporter that transfers zinc ions out of intestinal epithelial cells and into the blood is the zinc transporter 1 (ZnT1), the only member of the zinc transporter (ZnT) family that is located on the basement membrane and is widely distributed throughout numerous tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Passive (alternate and endocytic routes) and particularly active transport play critical roles in maintaining zinc homeostasis. , One of the zinc transporters engaged in active transport, known as Zrt-, Irt-like proteins (ZIPs), serves as a mediator for the process of zinc entering small intestinal epithelial cells through the apical membrane. The primary regulator of this mechanism is ZIP4. , Moreover, divalent metal transporter 1 (DMT1) is expressed in duodenal crypt cells and is also involved in transporting several metal ions into intestinal epithelial cells . There are four distinct metallothionein (MT) isoforms, among which MT1 is found in all organs and is responsible for transporting zinc from the apical membrane to the basement membrane within small intestine epithelial cells .…”

Section: Introductionmentioning

confidence: 99%

Structural Characterization of Zinc–Sucrose Complex and Its Ability to Promote Zinc Absorption in Caco-2 Monolayer Cells and Mice

Wang

Deng

et al. 2023

J. Agric. Food Chem.

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Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc−sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy−energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc−sucrose complex increased the amount of zinc uptake, retention, and transport in a dose-and timedependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc−sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl 2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc−sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl 2 . Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc−sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc−sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc−sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.

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