Nitric oxide (NO) is known to down-regulate drug-metabolizing cytochrome P450 enzymes in an enzyme-selective manner. Ubiquitin–proteasome-dependent and -independent pathways have been reported. Here, we studied the regulation of expression of human CYP51A1, the lanosterol 14α-demethylase required for synthesis of cholesterol and other sterols in mammals, which is found in every kingdom of life. In Huh7 human hepatoma cells, treatment with NO donors caused rapid post-translational down-regulation of CYP51A1 protein. Human NO synthase (NOS)-dependent down-regulation was also observed in cultured human hepatocytes treated with a cytokine mixture and in Huh7 cells expressing human NOS2 under control of a doxycycline-regulated promoter. This down-regulation was partially attenuated by proteasome inhibitors, but only trace levels of ubiquitination could be found. Further studies with inhibitors of other proteolytic pathways suggest a possible role for calpains, especially when the proteasome is inhibited. NO donors also down-regulated CYP51A1 mRNA in Huh7 cells, but to a lesser degree, than the down-regulation of the protein.
-
Cover Image
Cover Image
The 26S proteasome. Image kindly provided by Professor Joel Kowit from his work Degradation, a depiction in stained glass of the 26S proteasome (see http://joelkowit.com). In this issue of the Biochemical Journal, VerPlank and Goldberg describe how phosphorylation of the proteasome regulates protein breakdown by reviewing the ability of several kinases to alter proteasome function; see pages 3355–3371 for further details.
Nitric oxide stimulates cellular degradation of human CYP51A1, the highly conserved lanosterol 14α-demethylase Available to Purchase
Ji Won Park, Aria Byrd, Choon-myung Lee, Edward T. Morgan; Nitric oxide stimulates cellular degradation of human CYP51A1, the highly conserved lanosterol 14α-demethylase. Biochem J 1 October 2017; 474 (19): 3241–3252. doi: https://doi.org/10.1042/BCJ20170459
Download citation file:
Sign in
Sign in to your personal account
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |