Influence of biological sex on exercise-induced nuclear factor erythroid 2-related factor 2 and downstream targets

Abstract

Objective: The aim was to evaluate whether exercise induces different nuclear factor erythroid 2-related factor 2 (NRF2) responses in males and females. Methods: Twenty-two males and females (n = 11 per group; mean (s.d.): age: 25 (6) years, height: 1.71 (0.10) m, weight: 69.6 (12.3) kg) performed 100 drop jumps and 50 squat jumps. NRF2/antioxidant response element (ARE) binding in peripheral blood mononuclear cells, glutathione peroxidase (GPX) activity, and immune markers influenced by NRF2 (interleukin 6 (IL-6), tumour necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), total leukocytes, neutrophils, monocytes) were measured pre-exercise, post exercise, and 1 h post exercise. Results: NRF2/ARE binding did not significantly alter following exercise (P = 0.59), and no sex differences were evident (P = 0.17). Similarly, GPX activity did not change post exercise (P = 0.74) and did not differ between sexes (P = 0.61). IL-6 and TNF-α did not increase post exercise (P > 0.05 for both) but were lower in females (P < 0.01 for both). MMP-9 increased post exercise (P = 0.02), but no group differences were found (P = 0.27). VCAM-1 was unchanged after exercise (P = 0.38) and did not differ between groups (P = 0.11). Total leukocytes, neutrophils, and monocytes all increased post exercise (P < 0.01 for all); neutrophils were lower (P < 0.01), and monocytes were higher (P = 0.03) in females vs males. Conclusion: There were no sex differences in NRF2 activity at rest and in response to an exercise bout; however, several immune markers displayed sex-specific differences, independent to NRF2. Pre-registration: Open Science Framework = osf.io/5fpvn; Thorley, J., & Clifford, T. (2022, August 12). Curcumin supplementation, exercise, Nrf2/NFkB activity. https://doi.org/10.17605/OSF.IO/C4UQ2. Identifier: osf-registrations-c4uq2-v1 Significance statement Sex differences in NRF2 signaling were not evident, suggesting males and females may incur similar redox-specific adaptations post exercise.

Keywords

• exercise
• free radicals
• oxidative stress
• redox balance