Multiple forms of rat stomach histidine decarboxylase may reflect posttranslational activation of the enzyme.
Histidine decarboxylase (HDC) catalyzes the formation of histamine, which takes part in a variety of physiological processes including gastric acid secretion, neurotransmission and inflammation. While purified rat HDC is a homodimer of approximately 54 kDa subunits, molecular cloning of mammalian HDC has revealed that HDC mRNA encodes a 74 kDa protein. This discrepancy in molecular mass may be due to a posttranslational processing of the primary translated product of rat HDC mRNA. In the present study we demonstrate that full-length rat HDC expressed in Escherichia coli or in an in vitro transcription/translation system is enzymatically inactive, while expression of a C-terminus truncated HDC (reducing the molecular mass to 54 kDa) gave rise to a protein with high enzyme activity in the same expression systems. COS-7 cells expressing truncated HDC displayed high HDC activity, whereas COS-7 cells expressing full-length HDC displayed low activity. Western blot analysis of fetal rat liver and oxyntic mucosa of gastrin-stimulated rats revealed the presence of both full-length HDC (approximately 73 kDa) and a approximately 53 kDa subunit form in addition to an intermediate form of about 63 kDa. The results are in line with the view that rat HDC may be produced as an enzymatically inactive proenzyme which is processed to give rise to the active enzyme.
Dartsch
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C
Department of Physiology and Neuroscience, University of Lund, Sweden.
Chen
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D
Persson
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L
D000818:Animals; D019556:COS Cells; D004622:Embryo, Mammalian / Q000201:enzymology; D004789:Enzyme Activation / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D006640:Histidine Decarboxylase / Q000737:chemistry*; D007527:Isoenzymes / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics; D013270:Stomach / Q000201:enzymology*; D014162:Transfection / Q000235:genetics
D007527:Isoenzymes; D011994:Recombinant Proteins; D006640:Histidine Decarboxylase