Nrf2 up-regulates the induction of acidic sphingomyelinase by electrophiles

In this study, we clarified the involvement of NF-E2-related factor 2 (Nrf2) in the induction of ASMase mRNA by DEM. Promoter analysis using a series of deletion mutants of the human ASMase gene showed that ARE-like element1 located in a region between –200 and –160 bp upstream of the transcription start point is mainly a DEM-responsive element. Moreover, an electrophoretic mobility shift assay using ARE-like element1 revealed that Nrf2 is a candidate transcription factor that binds to ARE-like element1 in response to DEM. Finally, alteration of Nrf2 expression by overexpression and knockdown could regulate the induction of ASMase mRNA by DEM. This is the first evidence that supports the possibility that sphingolipid metabolism is affected via the induction of ASMase by the Nrf2 pathway.

Source: Journal of Biochemistry - July 28, 2015 Category: Biochemistry Authors: Kumagai, T., Kozakai, Y., Ishino, T., Yajima, Y., Nakagawa, Y., Imai, H. Tags: Regular Papers Source Type: research