TY - JOUR
T1 - Tissue distribution, intracellular localization and proteolytic processing of rat 4-hydroxyphenylpyruvate dioxygenase
AU - Neve, Søren
AU - Aarenstrup, Lene
AU - Tornehave, Ditte
AU - Rahbek-Nielsen, Henrik
AU - Corydon, Thomas Juhl
AU - Roepstorff, Peter
AU - Kristiansen, Karsten
N1 - Keywords: 4-Hydroxyphenylpyruvate Dioxygenase; Animals; Antibodies; Brain; Cloning, Molecular; DNA, Complementary; Gene Expression Regulation, Enzymologic; Hepatocytes; Immunochemistry; In Situ Hybridization; Kidney; Liver; Mass Spectrometry; Microscopy, Confocal; Microscopy, Immunoelectron; Molecular Sequence Data; Purkinje Cells; RNA, Messenger; Rats; Rats, Sprague-Dawley; Sequence Analysis, DNA
PY - 2003
Y1 - 2003
N2 - 4-hydroxyphenylpyruvate dioxygenase (HPD) is an important enzyme involved in tyrosine catabolism. HPD was shown to be identical to a protein named the F-antigen, exploited by immunologists because of its unique immunological properties. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. Decreased expression of HPD is often observed in association with the severe type I tyrosinemia, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. In this study we present a comprehensive analysis of tissue specific expression and intracellular localization of HPD in the rat. By combined use of in situ hybridization and immunohistochemistry we confirm previously known sites of expression in liver and kidney. In addition, we show that HPD is abundantly expressed in neurons in the cortex, cerebellum and hippocampus. By using immunoelectron microscopy and confocal laser scanning microscopy, we provide evidence that HPD contrary to earlier assumptions specifically localizes to membranes of the endoplasmic reticulum and the Golgi apparatus. Detailed mass spectrometric analyses of HPD purified from rat liver revealed N-terminal and C-terminal processing of HPD, and expression of recombinant HPD suggested that C-terminal processing enhances the enzymatic activity.
AB - 4-hydroxyphenylpyruvate dioxygenase (HPD) is an important enzyme involved in tyrosine catabolism. HPD was shown to be identical to a protein named the F-antigen, exploited by immunologists because of its unique immunological properties. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. Decreased expression of HPD is often observed in association with the severe type I tyrosinemia, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. In this study we present a comprehensive analysis of tissue specific expression and intracellular localization of HPD in the rat. By combined use of in situ hybridization and immunohistochemistry we confirm previously known sites of expression in liver and kidney. In addition, we show that HPD is abundantly expressed in neurons in the cortex, cerebellum and hippocampus. By using immunoelectron microscopy and confocal laser scanning microscopy, we provide evidence that HPD contrary to earlier assumptions specifically localizes to membranes of the endoplasmic reticulum and the Golgi apparatus. Detailed mass spectrometric analyses of HPD purified from rat liver revealed N-terminal and C-terminal processing of HPD, and expression of recombinant HPD suggested that C-terminal processing enhances the enzymatic activity.
U2 - 10.1016/S1065-6995(03)00117-3
DO - 10.1016/S1065-6995(03)00117-3
M3 - Journal article
C2 - 12867153
SN - 1065-6995
VL - 27
SP - 611
EP - 624
JO - Cell Biology International
JF - Cell Biology International
IS - 8
ER -