Disease relevance of Rhbdf1

• In contrast, LPS-treated C57BL/6 NOS2-deficient (NOS2-/-) mice did not benefit from the protective effect of Dist A on mortality from endotoxemia [1].
• Treatment with Dist A resulted in protection from hypotension in LPS-treated WT mice, but not in NOS2-/- mice [1].

High impact information on Rhbdf1

• Furthermore, LPS-induced NOS2 expression was attenuated in vivo (WT murine tissues) and in vitro (primary peritoneal and RAW 264.7 murine macrophages) with addition of Dist A [1].
• Therefore, we hypothesized that Dist A would attenuate NOS2 up-regulation in vivo during endotoxemia and improve animal survival [1].
• Dist A selectively decreased IFN regulatory factor-1 DNA binding in the enhancer region of the NOS2 promoter, and this IFN regulatory factor-1 site is critical for the effect of Dist A in attenuating LPS induction of NOS2 [1].
• Distamycin A (Dist A) belongs to a class of drugs termed minor-groove DNA binders, which can inhibit transcription factor binding to AT-rich regions of DNA [1].
• Characterization and comparison of the human and mouse Dist1/alpha-globin complex reveals a tightly packed multiple gene cluster containing differentially expressed transcription units [2].

References