Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not

Area of Science:

• Biochemistry
• Cellular Biology
• Nutritional Science

Background:

• Selenium (Se) and vitamin E are crucial antioxidant micronutrients.
• Selenium's function is mediated by selenoproteins, while vitamin E directly neutralizes oxidizing molecules in cell membranes.
• The interplay between these micronutrients and the Nrf2-antioxidant response element (ARE) pathway is not fully understood.

Purpose of the Study:

• To investigate the relationship between selenium and vitamin E deficiencies and the Nrf2-ARE pathway.
• To determine the specific roles of these micronutrients in regulating antioxidant and xenobiotic metabolizing enzymes.
• To elucidate whether these nutrient-specific defense mechanisms are independent.

Main Methods:

• Utilized ARE-reporter mice and Nrf2 knockout (Nrf2-/-) mice.
• Administered Se-deficient (0 Se), vitamin E-deficient (0 E), or control diets to weanling male mice for 16 or 22 weeks.
• Measured ARE reporter activity and levels of antioxidant enzymes like glutathione S-transferase (GST), NAD(P)H quinone oxidoreductase (NQOR), and heme oxygenase-1 (HO-1).

Main Results:

• Se deficiency significantly elevated ARE reporter activity (450-fold) and induced antioxidant enzymes (GST, NQOR, HO-1) in the liver.
• Vitamin E deficiency did not elevate ARE reporter activity or induce these specific antioxidant enzymes.
• Nrf2 deletion partially affected enzyme induction, abolishing GST induction but not NQOR and HO-1, indicating Nrf2-dependent and independent pathways.

Conclusions:

• Selenium deficiency, unlike vitamin E deficiency, triggers oxidative stress responses mediated by the Nrf2-ARE pathway and other stress-response pathways.
• The induction of antioxidant enzymes is differentially regulated by selenium and vitamin E.
• These findings suggest that the antioxidant defense systems involving selenium and vitamin E operate independently.