Regular Article
Enzyme-Specific Transport of Rat Liver Cytochrome P450 to the Golgi Apparatus

https://doi.org/10.1006/abbi.1996.0415Get rights and content

Abstract

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 withcis-Golgi, one highly enriched withtrans-Golgi, and one intermediate Golgi fraction representingmedial-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.

References (0)

Cited by (48)

  • CYP2E1 autoantibodies in liver diseases

    2014, Redox Biology
    Citation Excerpt :

    Beside DC, antigen presentation might also involve hepatic stellate cells [59] and possibly hepatocytes themselves, as pro-inflammatory cytokines have been shown to induce the hepatocyte expression of class II major histocompatibility complex (MHC) and co-stimulatory CD80 (B7.1) molecules [60]. Although during chronic liver injury CYP released from damaged hepatocytes might be a trigger for the breaking of self-tolerance, it should be noted that anti-CYP self-reactivity associated to CHC, alcohol abuse or adverse drug reactions is highly specific to individual CYPs [7–10] and there is no cross-reactivity between anti-CYP2E1 and anti-CYP2D6 antibodies [54,55] in HCV-infected patients. This indicates that additional and more specific mechanisms are likely involved.

  • Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress

    2010, Journal of Biological Chemistry
    Citation Excerpt :

    Additionally, a large number of studies implicate a role for CYP2E1 in reactive oxygen species (ROS) production and oxidative stress (7–11). A large fraction of hepatocellular CYP2E1 is located in the endoplasmic reticulum (ER), although significant levels are detected in other cell compartments including lysosomes (12), plasma membrane (13, 14), Golgi apparatus (15), peroxisomes (16), and mitochondria (17–20). Studies have shown increased mitochondrial CYP2E1 content in streptozotocin-treated and alcohol-treated rats and mice (21, 22).

  • CYP2E1 and oxidative liver injury by alcohol

    2008, Free Radical Biology and Medicine
View all citing articles on Scopus

This research was supported by grants from the Swedish Alcohol Research Fund and from the Swedish Medical Research Council.

2

To whom correspondence should be addressed at Department of Medical Biochemistry and Biophysics, Berzelius Laboratory, Karolinska institutet, S-171 77 Stockholm, Sweden. Fax: 46-833-8453. E-mail: [email protected].

View full text