Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells

Area of Science:

• Biochemistry
• Molecular Biology
• Hepatology

Background:

• Glutathione (GSH) is recognized for its liver antioxidant and detoxifying properties.
• The precise mechanisms of GSH's hepatoprotective effects, including NRF2 activation, require further elucidation.
• Comparative analyses of GSH's regulatory roles under physiological and oxidative stress are lacking.

Purpose of the Study:

• To comprehensively analyze the biological events regulated by Glutathione (GSH) under both physiological and oxidative stress conditions.
• To compare the effects of GSH alone versus GSH in combination with hydrogen peroxide (HP) induced oxidative stress.
• To identify key signaling pathways and biological processes modulated by GSH.

Main Methods:

• DNA microarray analysis was employed.
• Four experimental groups were established: Control, GSH, hydrogen peroxide (HP), and GSH + HP.
• Gene expression profiles were compared across these groups.

Main Results:

• GSH treatment upregulated genes related to cell proliferation, growth, differentiation (MAPK pathway), and liver functions (alcohol and cholesterol metabolism).
• Under HP-induced oxidative stress, GSH significantly activated cell proliferation, cell cycle, and signaling pathways (TGFβ, MAPK, PI3K/AKT, HIF-1).
• GSH downregulated disease-related pathways, including chemical carcinogenesis and fibrosis, in the presence of oxidative stress.

Conclusions:

• GSH exhibits distinct regulatory effects on gene expression under physiological and oxidative stress.
• GSH promotes cellular growth and liver function physiologically and provides significant protection against oxidative damage.
• These findings support the potential use of GSH as a supplement for managing oxidative stress-related conditions.