Gpx1-flox Mouse

Glutathione peroxidase 1 (GPX1), the first identified selenoprotein, is a widely expressed antioxidant enzyme. It uses glutathione as a substrate to catalyze hydrogen peroxide, lipid peroxide, and peroxynitrite, reducing intracellular oxidative stress. The GPX1 gene is regulated at transcriptional, post-transcriptional, and translational levels and participates in multiple signaling pathways, influencing cell proliferation, apoptosis, invasion, immune response, and chemoresistance [2].

In cancer research, high GPX1 expression is associated with poor survival in acute myeloid leukemia (AML) patients, linking to immunosuppression. GPX1 expression positively correlates with myeloid-derived suppressor cells (MDSCs), monocytes, T-cell exhaustion, MDSC-promoting CCR2, and immune inhibitory checkpoints, while negatively with CD4+ and CD8+ T cells. Silencing GPX1 reduces AML cell viability and CCR2 expression [1].

In laryngeal squamous cell carcinoma (LSCC), high GPX1 expression is correlated with lymph node metastasis, TNM stage, and worse prognosis, and is an independent prognostic factor [3].

In brain lower-grade glioma (LGG), GPX1 overexpression is significantly correlated with poor prognosis, and is an independent predictive factor. High GPX1 expression links to a shorter overall survival (OS), and the interaction between GPX1 and chemoradiotherapy exhibits a beneficial clinical effect. GPX1 is also negatively correlated with the half-inhibition concentration (IC50) of temozolomide (TMZ) [4].

In kidney cancer, high GPX1 levels are positively correlated with short OS, distant metastasis, lymphatic metastasis, and tumor stage, and GPX1 may serve as a diagnostic and prognostic biomarker [7]. Additionally, the GPX1 Pro198Leu polymorphism is associated with a significantly increased risk of bladder cancer [8].

In the context of aging, GPX1 knockout (GPX1-/-) in mice causes accelerated age-related cataracts, indicating that GPX1 is more critical than catalase for lens transparency, optical quality, and homeostasis in the aging lens [5].

In Crohn's disease, monocyte-derived macrophages from individuals with active disease have increased susceptibility to H2O2-induced ferroptosis cell death, potentially due to reduced GPX1 expression [6].

In conclusion, GPX1 is a crucial antioxidant enzyme with significant roles in various biological processes and disease conditions. Studies using gene knockout models, especially in cancer, aging-related cataracts, and Crohn's disease, have revealed its importance in disease development, prognosis, and potential as a therapeutic target.