Enzyme-specific transport of rat liver cytochrome P450 to the Golgi apparatus.
It has been reported that cytochrome P450 is expressed in the plasma membrane of hepatocytes isolated from human and rat. Cytochrome P450s expressed on the cell surface are potential targets for the immune response of drug-induced and autoimmune hepatitis. However, the mechanisms behind transport of cytochrome P450 to the plasma membrane are obscure. The present investigation aimed at identifying cytochrome P450 expressed in the Golgi apparatus. Golgi membrane fractions from rat liver were prepared and characterized: one enriched with cis-Golgi, one highly enriched with trans-Golgi, and one intermediate Golgi fraction representing medial-Golgi. In these three fractions, significant amounts of cytochrome P450 and NADPH cytochrome P450 reductase were present, which could not be accounted for by contamination with endoplasmic reticulum. A marked difference between the relative content of different cytochrome P450 enzymes was found. CYP4A1 was found at the highest concentration, CYP2E1 at an intermediary level, and CYP1A2 at low levels, whereas no Golgi-specific CYP3A1 was detectable. It was also shown that the CYP2E1 present in the Golgi fractions was catalytically active. It is suggested that various forms of hepatic cytochrome P450 are transported to the plasma membrane through the Golgi apparatus in an enzyme-specific manner.
Neve
E P
EP
Department of Medical Biochemistry and Biophysics, Karolinska institutet, Stockholm, Sweden. etienne.neve@mbb.ki.se
Eliasson
E
E
Pronzato
M A
MA
Albano
E
E
Marinari
U
U
Ingelman-Sundberg
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002458:Cell Fractionation; D002462:Cell Membrane / Q000201:enzymology; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; C465138:Cyp3a23-3a1 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D042926:Cytochrome P-450 CYP4A; D009251:NADPH-Ferrihemoprotein Reductase