@entity1255 downregulates gene expression of XXXX in hepatocytes.

@entity1560 @entity10182 @entity1255 @entity19 @entity409 @entity71730 @entity5784 @entity1853 @entity1234 @entity1575 @entity3562 @entity10183 @entity1865
BACKGROUND: @entity3562 ( @entity3562 ) is an independent risk factor for @entity409 , such as @entity1560 and @entity1575 . However, the mechanisms underlying this pro-oxidative effect of @entity1255 ( @entity5784 ) in hepatocytes remain largely unknown. Thus, we investigated the effect of @entity5784 on the gene expression of @entity10183 ( @entity10183 ), the primary rate-limiting enzyme in heme catabolism and a key anti-oxidant detoxification enzyme in maintaining cellular redox homeostasis. METHODS: In vivo, twenty male C57BL/6 @entity19 at 8  weeks of age were randomly divided into two groups. One group was fed a chow diet (chow group; n   =   10), the other group of @entity19 was fed a @entity1853 -supplemented diet (Met group, 1  mg  kg(-1)  day(-1)  @entity1853 in drinking water; n   =   10) for 4  weeks. In vitro, HepG2 cells were stimulated with different doses of @entity1255 ( @entity5784 ). RESULTS: Four weeks' @entity1853 supplementation caused a significant increase of plasma @entity5784 concentration and a decrease of @entity10183 expression in the liver of C57BL/6 @entity19 than @entity19 received chow diet. Besides, SOD enzyme activities were impaired and the level of oxidative stress markers, such as @entity1234 ( @entity1865 ) were elevated in the liver from @entity19 supplemented with @entity1853 compared with control @entity19 . In cultured hepatocytes, @entity5784 treatment reduced both the mRNA and protein levels of @entity10183 dose-dependently. However, @entity5784 had no effect on the gene expression of @entity10182 , the major transcriptional regulator of @entity10183 . Instead, @entity5784 induced the expression of @entity71730 , a transcriptional repressor of @entity10183 . In addition, @entity5784 stimulated the nuclear localization of @entity71730 but prevented that of @entity10182 . Furthermore, we found that knockdown of @entity71730 attenuated the suppression of the @entity10183 expression by @entity5784 . CONCLUSIONS: Collectively, our results demonstrated that @entity71730 plays an important role in @entity5784 -triggered ROS generations through inhibiting @entity10183 expression, likely, resulting from the disturbed interplay between @entity71730 and @entity10182 .
