Disease relevance of CYP2S1

• P450 expression was also detected in ovarian cancer metastasis and CYP2S1 and P450 reductase both showed significantly increased expression in metastasis compared with primary ovarian cancer [1].
• In contrast to the positive controls, i.e., CHO cells expressing human CYP2A13 (for NNK activation) or human CYP1A1 (for BaP activation), there was no increase in NNK- or BaP-induced toxicity in the CHO cells expressing CYP2S1 [2].
• We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis [3].

High impact information on CYP2S1

• We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme [3].
• METHODS: We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29) [3].
• Recombinant enzymes overexpressed in bacteria show broad catalytic specificity of human cytochrome P450 2W1 and limited activity of human cytochrome P450 2S1 [4].
• High expression of CYP51 or CYP2S1 were associated with poor prognosis and CYP51 is an independent marker of prognosis [5].
• The SCD and CYP2S1 genes function in lipid metabolism [6].

Chemical compound and disease context of CYP2S1

• Regarding their metabolism of xenobiotics, much remains to be established, but CYP2S1 metabolizes naphthalene and it is likely that these P450s are responsible for metabolic activation of several different kinds of xenobiotic chemicals and contribute to extrahepatic toxicity and carcinogenesis [7].

Biological context of CYP2S1

• These results clearly demonstrate that CYP2S1 does not catalyze the metabolism of nicotine and the metabolic activation of these lung carcinogens [2].
• Identification and tissue distribution of the novel human cytochrome P450 2S1 (CYP2S1) [8].
• The full-length CYP2S1 cDNA was amplified by nested polymerase chain reaction from a human lung cDNA library and was expressed in both Chinese hamster ovary (CHO) cells and Sf9 insect cells [2].
• The predicted 504 amino acid sequence displays 38--49% identity with CYP2 family members and the protein was designated CYP2S1. mRNA dot blot analysis demonstrated high expression levels in trachea, lung, stomach, small intestine, and spleen [8].
• Identification of genetic polymorphisms of CYP2S1 in a Finnish Caucasian population [9].

Anatomical context of CYP2S1

• Since CYP2S1 is predominantly expressed in human lung and trachea, it is reasonable to speculate that CYP2S1 may play an important role in metabolizing the environmental chemicals to which human respiratory tissues are exposed [2].
• Subcellular fractionation and immunostaining revealed that CYP2S1 was localized in the endoplasmic reticulum [8].
• Nor does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1, or any of the cytochrome P450 enzymes present in the human liver microsomes [10].
• CYP2S1 was also inducible in a human lung epithelial cell line [11].

Associations of CYP2S1 with chemical compounds

• The heterologously expressed CYP2S1 proteins showed no detectable activity in metabolizing nicotine and PhIP [2].
• In the present study, we examined the activity of human CYP2S1 in the metabolism of nicotine and in the activation of three potent carcinogens in cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), benzo[a]pyrene (BaP), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) [2].
• In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene [12].

Regulatory relationships of CYP2S1

• We conclude that CYP2S1 represents a novel abundantly expressed human P450 with potential importance for extrahepatic xenobiotic metabolism [8].

Other interactions of CYP2S1

• The presence of strong CYP51 (log-rank = 12.11, P = 0.0005) or strong CYP2S1 (log-rank = 6.72, P = 0.0095) immunoreactivity were associated with poor prognosis [5].
• CYP2S1 has been shown to metabolize all-trans retinoic acid and CYP2R1 is a major vitamin D 25-hydroxylase [7].

Analytical, diagnostic and therapeutic context of CYP2S1

• Western blot analysis, using an antiserum directed against the C-terminus of the enzyme, detected a protein in human lung with the same mobility as recombinant CYP2S1 [8].
• INTERPRETATION: These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis [3].
• In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays [13].

References