Nitric oxide and interleukin-1β stimulate the proteasome-independent degradation of the retinoic acid hydroxylase CYP2C22 in primary rat hepatocytes

• Published in: The Journal of pharmacology and experimental therapeutics 2014-01, Vol.348 (1), p.141-152
• Main Authors: Lee, Choon-myung, Lee, Bang-sub, Arnold, Samuel L, Isoherranen, Nina, Morgan, Edward T
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - genetics; Down-Regulation - physiology; HEK293 Cells; Hepatocytes - drug effects; Hepatocytes - enzymology; Humans; Interleukin-1beta - physiology; Male; Metabolism, Transport, and Pharmacogenomics; Mixed Function Oxygenases - metabolism; Molecular Sequence Data; Nitric Oxide - physiology; Nitric Oxide Donors - pharmacology; Primary Cell Culture; Proteasome Endopeptidase Complex - physiology; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Tretinoin - metabolism
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.113.209841

CYP2C22 was recently described as a retinoic acid-metabolizing cytochrome P450 enzyme whose transcription is induced by all-trans-retinoic acid (atRA) in hepatoma cells (Qian L, Zolfaghari R, and Ross AC (2010) J Lipid Res 51:1781-1792). We identified CYP2C22 as a putative nitric oxide (NO)-regulated protein in a proteomic screen and raised specific polyclonal antibodies to CYP2C22 to study its protein expression. We found that CYP2C22 is a liver-specific protein that was not significantly induced by activators of the pregnane X receptor, constitutive androstane receptor, or peroxisome proliferator-activated receptor-α, but was downregulated to