Protective role of the placental efflux transporter BCRP/ABCG2 in the relationship between prenatal cadmium exposure, placenta weight, and size at birth

Barrett, Emily S.; Rivera‐Núñez, Zorimar; Getz, Kylie; Ohman‐Strickland, Pamela; Zhang, Ranran; Kozlosky, Danielle; Doherty, Cathleen; Buckley, Brian; Brunner, Jessica; Miller, Richard K.; O’Connor, Thomas G.; Aleksunes, Lauren M.

doi:10.1016/j.envres.2023.115597

Cited by 7 publications

(1 citation statement)

References 73 publications

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“…Placental ABCG2/BCRP seems to be negatively affected by Cd, which reduces functional activity, though not necessary in parallel with attenuated expression (Kummu et al 2012 ; Liu et al 2016 ). Moreover, infants harboring the reduced function ABCG2/BCRP polymorphism C421A (Q141K) suffered from retarded fetal development, smaller placentas and increased placental Cd (Barrett et al 2023 ). In ABCG2/BCRP-overexpressing HEK293 cells treated with 0.5 µM CdCl 2 for 30 min and incubated for 60 min after Cd washout, less Cd was accumulated compared to empty vector.…”

Section: Abc Transporters and CDmentioning

confidence: 99%

Cadmium transport by mammalian ATP-binding cassette transporters

Thévenod,

Lee

2024

Biometals

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Cellular responses to toxic metals depend on metal accessibility to intracellular targets, reaching interaction sites, and the intracellular metal concentration, which is mainly determined by uptake pathways, binding/sequestration and efflux pathways. ATP-binding cassette (ABC) transporters are ubiquitous in the human body—usually in epithelia—and are responsible for the transfer of indispensable physiological substrates (e.g. lipids and heme), protection against potentially toxic substances, maintenance of fluid composition, and excretion of metabolic waste products. Derailed regulation and gene variants of ABC transporters culminate in a wide array of pathophysiological disease states, such as oncogenic multidrug resistance or cystic fibrosis. Cadmium (Cd) has no known physiological role in mammalians and poses a health risk due to its release into the environment as a result of industrial activities, and eventually passes into the food chain. Epithelial cells, especially within the liver, lungs, gastrointestinal tract and kidneys, are particularly susceptible to the multifaceted effects of Cd because of the plethora of uptake pathways available. Pertinent to their broad substrate spectra, ABC transporters represent a major cellular efflux pathway for Cd and Cd complexes. In this review, we summarize current knowledge concerning transport of Cd and its complexes (mainly Cd bound to glutathione) by the ABC transporters ABCB1 (P-glycoprotein, MDR1), ABCB6, ABCC1 (multidrug resistance related protein 1, MRP1), ABCC7 (cystic fibrosis transmembrane regulator, CFTR), and ABCG2 (breast cancer related protein, BCRP). Potential detoxification strategies underlying ABC transporter-mediated efflux of Cd and Cd complexes are discussed.

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Section: Abc Transporters and CDmentioning

confidence: 99%