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Lymphocyte cytochrome P450-CYP2E1 expression in human IDDM subjects
M P Hannon-Fletcher1, M J O'Kane, K W Moles
1Cancer and Ageing Research Group, University of Ulster, Cromore Road, Coleraine, County Londonderry BT52 1SA, UK. mp.hannon@ulst.ac.uk
Insights
Levels of Cytochrome P450 2E1 (CYP2E1) were significantly elevated in the lymphocytes of individuals with insulin-dependent diabetes mellitus (IDDM). This increased CYP2E1 expression may contribute to oxidative stress in IDDM patients.
Area of Science:
- Biochemistry
- Immunology
- Metabolic Disorders
Background:
- Cytochrome P450 2E1 (CYP2E1) is a phase I enzyme implicated in various metabolic processes.
- Previous studies indicated CYP2E1 induction in diabetic and obese animal models, and elevated levels in children with IDDM.
- Oxidative stress is a known factor in the development of diabetic complications.
Purpose of the Study:
- To investigate CYP2E1 expression in peripheral blood lymphocytes of well-controlled IDDM subjects compared to healthy controls.
- To assess the relationship between CYP2E1 levels, glycemic control (HbA1c), and duration of IDDM.
Main Methods:
- Western blot analysis was employed to quantify CYP2E1 levels.
- Phoretix image analysis was used for quantitative assessment of protein expression.
- Peripheral blood lymphocytes were isolated from eight IDDM patients and eight age- and sex-matched controls.
Main Results:
- CYP2E1 levels were low to undetectable in lymphocytes from healthy control subjects.
- A significant elevation (mean 3.1-fold) of CYP2E1 was observed in lymphocytes from IDDM subjects.
- No correlation was found between elevated CYP2E1 levels and HbA1c or duration of IDDM, but inter-individual variations were noted.
Conclusions:
- CYP2E1 expression is upregulated in lymphocytes of IDDM patients, even with good metabolic control.
- Elevated CYP2E1 in IDDM lymphocytes may exacerbate oxidative stress, potentially contributing to disease complications.
- Further research is warranted to explore the role of CYP2E1 modulation in IDDM pathogenesis.
Abstract:
Cytochrome P4502E1, a phase I enzyme, has been shown to be induced in liver samples from diabetic and obese rats. One study demonstrated elevated levels of CYP2E1 in children with IDDM, using Western blot analysis. The aim of this investigation was to determine CYP2E1 expression in peripheral blood lymphocytes from eight well-controlled IDDM and eight sex- and age-matched control subjects using Western blot analysis and Phoretix image analysis. Levels of CYP2E1 were low to undetectable in human lymphocytes from healthy control subjects. However, levels of CYP2E1 were elevated in lymphocytes from IDDM subjects (mean 3.1-fold higher). The elevated levels of CYP2E1 in the IDDM subjects showed no correlation with HbA(1c) nor duration of IDDM; however, there were marked inter-individual differences in levels of induction of CYP2E1 between all subjects. The results of this study suggest that in human IDDM subjects, even with good metabolic control, expression of CYP2E1 is elevated when compared to controls. CYP2E1 is known to generate ROS in vivo, the modulation of this isoform in lymphocytes from IDDM subjects, could well add to the oxidative stress associated with IDDM and the development of associated complications.
