|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|5558528||1561148||2017||8 صفحه PDF||سفارش دهید||دانلود رایگان|
- Cadmium is an environmentally prevalent toxicant.
- Little was known regarding the elimination and detoxification of cadmium.
- Cadmium ion is here demonstrated as a substrate of MATE transporters.
- MATEs may function as cellular elimination machinery in cadmium detoxification.
Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd2Â +). In this study, we aimed to examine whether Cd2Â + is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd2Â +. The cells overexpressing MATEs showed a 2-4 fold increase of Cd2Â + uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (Km) of 130Â Â±Â 15.8Â Î¼M for HEK-hMATE1; 139Â Â±Â 21.3Â Î¼M for HEK-hMATE2-K; and 88.7Â Â±Â 13.5Â Î¼M for HEK-mMate1, respectively. Cd2Â + could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC50) of 97.5Â Â±Â 6.0Â Î¼M, 20.2Â Â±Â 2.6Â Î¼M, and 49.9Â Â±Â 6.9Â Î¼M in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd2Â + out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd2Â +-induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd2Â + and may function as cellular elimination machinery in Cd intoxication.
Journal: Toxicology and Applied Pharmacology - Volume 314, 1 January 2017, Pages 55-62