Rapid changes in amino acid and polyamine metabolism during copper-induced cell death of human gingival fibroblast

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There are very few studies on the interaction between dental alloys and oral tissues. The effect of direct contact with copper (Cu) on the cellular function of human gingival fibroblast (HGF) derived from the periodontal tissues was investigated. When HGF cells were inoculated onto a Cu plate, the viability of HGF cells immediately declined. This was accompanied by vacuolization and chromatin condensation near the nuclear membrane. The intracellular concentration of spermidine and spermine declined, whereas that of putrescine slightly increased. Amino acid analysis of the medium revealed that glutamine was consumed at the greatest rate, amounting to more than half of the total amino acid consumption. Contact with the Cu plate resulted in the complete elimination of glutamine utilization and a simultaneous increase in the production of most amino acids, possibly due to enhanced proteolysis. This was accompanied by a time-dependent increase in the consumption of cystine, possibly due to oxidative reactions, and the enhanced production of glycine and glutamic acid. These data suggest that the contact with the Cu plate induced non-apoptotic cell death in HGF cells, which was tightly coupled with a rapid dysfunction of amino acid and polyamine metabolism. Dental alloys have been reported to occasionally induce allergic reactions in the oral cavity by the metal ions released from the alloys. The metal ions may be incorporated into the cells, possibly via metal transporter-mediated endocytosis. Numerous studies have shown cytotoxic activity and tissue-damaging activity of metal extracts. However, the biological impact of contact with metals is unclear. We recently developed an assay system to investigate the cytotoxicity induced in cultured cells by direct contact with metals. Using this system, we found that direct contact with a copper (Cu) plate induced non-apoptotic cell death, characterized by a smear pattern of DNA fragmentation and minor caspase activation, and vacuolization in a human promyelocytic leukemic cell line (HL-60), whereas other metals such as gold, silver and palladium were essentially inactive. Here, whether direct contact with Cu has a similar impact on cultured human gingival fibroblasts (HGF) derived from periodontal tissues was investigated.

identifier:JOS-0258851X-21-835

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