Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaußstraße 20, 42119, Wuppertal, Germany.
Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.
Mol Nutr Food Res. 2023 Mar;67(6):e2200283. doi: 10.1002/mnfr.202200283. Epub 2023 Feb 9.
Despite their essentiality, several studies have shown that either manganese (Mn) or zinc (Zn) overexposure may lead to detrimental health effects. Although Mn is transported by some of the SLC family transporters that translocate Zn, the role of Zn in hepatocellular Mn transport and Mn-induced toxicity have yet to be fully characterized.
The human hepatoma cell line, HepG2, is utilized. Total cellular Mn and Zn amounts are determined after cells are treated with Zn 2 or 24 h prior to Mn incubation for additional 24 h with inductively coupled plasma-based spectrometry and labile Zn is assessed with the fluorescent probe FluoZin-3. Furthermore, mRNA expression of genes involved in metal homeostasis, and mechanistic endpoints associated with Mn-induced cytotoxicity are addressed. These results suggest that Zn protects against Mn-induced cytotoxicity and impacts Mn bioavailability to a great extent when cells are preincubated with higher Zn concentrations for longer duration as characterized by decreased activation of caspase-3 as well as lactate dehydrogenase (LDH) release.
Zn protects against Mn-induced cytotoxicity in HepG2 cells possibly due to decreased Mn bioavailability. Additionally, mRNA expression of metal homeostasis-related genes indicates possible underlying pathways that should to be addressed in future studies.
尽管锰（Mn）和锌（Zn）是必需的微量元素，但已有多项研究表明，这两种元素的过度暴露都可能对健康产生有害影响。尽管一些 SLC 家族转运蛋白可转运 Zn，但 Mn 的转运机制仍有待进一步研究，此外，Zn 在肝细胞 Mn 转运和 Mn 诱导的毒性中的作用也尚未完全阐明。
本研究使用人肝癌细胞系 HepG2。用电感耦合等离子体质谱法（ICP-based spectrometry）测定细胞经 Zn 处理 2 或 24 小时后，再孵育 Mn 24 小时后的总细胞内 Mn 和 Zn 含量，并使用荧光探针 FluoZin-3 评估可利用的 Zn。此外，还研究了与金属稳态相关的基因的 mRNA 表达，以及与 Mn 诱导的细胞毒性相关的机制终点。这些结果表明，当细胞用更高浓度的 Zn 预孵育更长时间时，Zn 可保护细胞免受 Mn 诱导的细胞毒性，并且在很大程度上影响 Mn 的生物利用度，表现为 caspase-3 的激活和乳酸脱氢酶（LDH）释放减少。
Zn 可能通过降低 Mn 的生物利用度来保护 HepG2 细胞免受 Mn 诱导的细胞毒性。此外，金属稳态相关基因的 mRNA 表达表明，未来的研究应该关注可能的潜在途径。
