Mild ozonisation activates antioxidant cell response by the Keap1/Nrf2 dependent pathway

Area of Science:

• Biochemistry
• Molecular Biology
• Oxidative Stress Research

Background:

• Ozone therapy is an emerging adjuvant treatment with expanding applications.
• The precise molecular mechanisms behind ozone therapy's benefits remain incompletely understood.
• Existing evidence suggests a role for the Nuclear Factor Erythroid-derived 2-like 2 (Nrf2) pathway in mediating ozone's antioxidant effects.

Purpose of the Study:

• To elucidate the molecular mechanisms of low-dose ozone therapy.
• To investigate the role of the Nrf2 pathway in ozone-induced antioxidant responses.
• To provide mechanistic evidence for ozone's therapeutic effects.

Main Methods:

• Treatment of cultured cells with low-concentration ozone.
• Analysis of Nrf2 nuclear translocation to chromatin.
• Measurement of antioxidant response element (ARE)-driven gene expression.
• Utilizing ectopic expression of Kelch-like ECH associated protein (Keap1) as an Nrf2 inhibitor.

Main Results:

• Low-dose ozone exposure promoted Nrf2 nuclear translocation to active transcription sites.
• Ozone treatment significantly increased the expression of ARE-driven genes.
• Inhibition of Nrf2 by Keap1 reverted the ozone-induced ARE activation.

Conclusions:

• Low-dose ozone therapy effectively activates the Nrf2 pathway in cultured cells.
• The Nrf2 pathway is crucial for mediating the antioxidant response to mild ozonisation.
• This study provides a mechanistic link between ozone treatment and antioxidant gene expression.