ReviewCYP2S1: A short review
Section snippets
Identification of CYP2S1 in human and mouse
Cytochrome P450 (CYP) enzymes are involved in the oxidative metabolism of many endogenous molecules, such as steroids, fatty acids, eicosanoids, and retinoids, thereby participating in the maintenance of the body homeostasis (reviewed, e.g., by Nebert, 1991, Lewis, 2004). They also play a major role in the biotransformation of numerous exogenous compounds (xenobiotics). These include a wide range of important pharmacological drugs, such as antidepressants, neuroleptics, lipophilic
Regulation, induction, and metabolism
Many of the CYPs are not expressed constitutively, but are induced upon exposure to chemical compounds. The inducers are themselves usually substrates for these enzymes, thereby regulating their own biotransformation.
Tissue distribution of CYP2S1 expression
A majority of CYPs have their highest expression in the liver, which has a dominant role in the clearance of foreign compounds. However, many CYPs are also expressed in tissues other than the liver (Hukkanen et al., 2002, Ding and Kaminsky, 2003). Expression in the extrahepatic tissues may be of significance for the metabolism of exogenous substances, since these tissues are the major route of exposure, and thus also the potential target for harmful effects of the metabolites produced (Pelkonen
CYP2S1 expression during embryogenesis
There is growing evidence that some members of the CYP superfamily could be involved in the regulation of basic developmental processes such as pattern formation, morphogenesis, cell differentiation, and growth (Stoilov et al., 2001). As retinoids are known to be crucial for embryonic development (reviewed by Marill et al., 2003), those CYPs that are known to the participate in metabolism of retinoids, e.g., CYP1B1, CYP26, and now also CYP2S1, are of especial interest (Stoilov, 2001, Stoilov et
Genetic polymorphism of CYP2S1
The wide individual variation in metabolic capacity detected for many CYP enzymes may influence therapeutic efficacy and toxic side effects of drugs as well as individual susceptibility to chemical carcinogenesis (Raunio et al., 1995, Ingelman-Sundberg et al., 1999). Such variability has been found to be partly genetically determined. In fact, a majority of the CYP genes exhibit genetic polymorphisms (reviewed by Ingelman-Sundberg, 2004). In particular, many members of the CYP2 family, such as
Conclusions
CYP2S1 gene is a recently identified member of the CYP2 family, located on human chromosome 19q at the distal end of a cluster of CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. Despite apparently sharing a common ancestor and sequence homology with other CYP2 family members, CYP2S1 exhibits many features that have been thought to be characteristic to the CYP1 family members, such as dioxin-inducibility mediated by AHR and ARNT. Furthermore, the expression pattern of CYP2S1 has been
Note added in proof
While this paper paper was in press, high expression of CYP2S1 was reported to be associated with poor prognosis in colorectal cancer (Kumarakulasingham et al., 2005).
Acknowledgments
Our work was financially supported by the Academy of Finland (grant no. 52276), the Work Environment Fund (grant no. 100389), and NIH Grant RO1CA28868 and Underrepresented Minority Supplement S1 to this grant (SR).
References (58)
- et al.
Predictive value of comparative molecular field analysis modelling of naphthalene inhibition of human CYP2A6 and mouse CYP2A5 enzymes
Toxicol. In Vitro
(2003) - et al.
Comparative expression profiling of 40 mouse cytochrome P450 genes in embryonic and adult tissues
Arch. Biochem. Biophys.
(2003) - et al.
Expression patterns of mouse and human CYP orthologs (families 1–4) during development and in different adult tissues
Arch. Biochem. Biophys.
(2005) - et al.
Tissue- and cell type-specific expression of cytochrome P450 1A1 and cytochrome P450 1A2 mRNA in the mouse localized in situ hybridization
Biochem. Pharmacol.
(1999) - et al.
Epidermal CYP2 family cytochromes P450
Toxicol. Appl. Pharmacol.
(2004) - et al.
Identification of a 43-kDa protein in human liver cytosol that binds to the 3′-untranslated region of CYP2A6 mRNA
Biochem. Pharmacol.
(2001) - et al.
Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment
Trends Pharmacol. Sci.
(1999) - et al.
Novel extrahepatic cytochrome P450s
Toxicol Appl Pharmacol.
(2005) - et al.
Ultraviolet-B exposure of human skin induces cytochromes P450 1A1 and 1B1
J. Invest. Dermatol.
(2000) - et al.
Rat testosterone 7 alpha-hydroxylase. Isolation, sequence, and expression of cDNA and its developmental regulation and induction by 3-methylcholanthrene
J. Biol. Chem.
(1987)