The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Molecular mechanism of dihydropyrazine-induced cytotoxicity: the possibility of an independent pathway from the receptor for advanced glycation end products
Yuu MiyauchiMadoka SawaiTakumi IshidaHisao KansuiShinji Takechi
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2021 Volume 46 Issue 11 Pages 509-514


Dihydropyrazines (DHPs) are one of glycation products that are non-enzymatically generated in vivo and in food. We had previously revealed that 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), a methyl-substituted DHP, elicited redox imbalance and cytotoxicity in cultured cells. However, the molecular mechanisms underlying DHP-3-induced cytotoxicity remain unclear. To address this issue, we examined the involvement of the receptor for advanced glycation end products (RAGE) in DHP-3-induced cytotoxicity. To evaluate the role of RAGE, we prepared HeLa cells that constitutively expressed RAGE and its deletion mutant, which lacks the cytoplasmic domain (RAGEΔcyto), using an episomal vector. After transfection with the vector, cells were selected following incubation with multiple concentrations of hygromycin to remove non-transfected cells. The expression of RAGE and RAGEΔcyto in the cells was confirmed by immunoblotting. RAGE and RAGEΔcyto were apparently expressed in transfected cells; however, there were no significant differences in DHP-3-induced cytotoxicity between these cells and mock vector-transfected cells. These results suggested that DHP-3 elicits cytotoxicity in a RAGE-independent manner.

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© 2021 The Japanese Society of Toxicology
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