Regulation of L-histidine decarboxylase and its role in carcinogenesis.

Publisher Summary This chapter reviews important findings relating to the regulation of histidine decarboxylase (HDC) at the transcriptional and posttranslational levels and discusses the role of HDC or histamine in carcinogenesis. Histamine is a bioamine whose roles in allergy, inflammation, neurotransmission, and gastric acid secretion have been well described. Animal studies using mice deficient in histamine production have confirmed these important functions and identified a number of new ones. A single enzyme, L-histidine decarboxylase, is responsible for histamine biosynthesis in mammals. It is expressed in the liver of the developing fetus and in the stomach, brain, thymus, spleen, and bones of adults. At the transcription level, HDC gene expression is regulated by several stimuli, including gastrin (a stomach peptide hormone), lipopolysaccharide (LPS), phorbol 12-myristate-13-acetate (PMA), oxidative stress, and Helicobacter pylori infection. At the posttranslational level, processing into multiple truncated isoforms provides a cellular mechanism for controlling the activity of the actual enzyme. While these aspects of regulation are important for normal physiological function, histamine is increasingly being recognized as a contributory factor in the development of some cancer types.