Oxidative Stress Induces Mouse Follicular Granulosa Cells Apoptosis via JNK/FoxO1 Pathway

Area of Science:

• Cell Biology
• Molecular Biology
• Endocrinology

Background:

• c-Jun N-terminal protein kinase (JNK) regulates apoptosis.
• Forkhead box O (FoxO) transcription factors are vital for cell metabolism, apoptosis, and cell cycle.
• The specific role of the JNK/FoxO1 pathway in oxidative stress-induced apoptosis is not fully understood.

Purpose of the Study:

• To investigate the role of the JNK/FoxO1 pathway in oxidative stress-induced apoptosis in mouse follicular granulosa cells (MGCs).

Main Methods:

• Assessed JNK activity in MGCs under oxidative stress.
• Utilized SP600125, a selective JNK inhibitor, to evaluate its effect on apoptosis.
• Examined FoxO1 nuclear translocation and its interaction with 14-3-3 proteins.
• Investigated the regulation of FoxO1 expression via JNK signaling.

Main Results:

• JNK activity significantly increased in response to oxidative stress in MGCs.
• SP600125 inhibited oxidative stress-induced MGCs apoptosis.
• Oxidative stress promoted FoxO1 nuclear translocation through JNK activation.
• JNK mediated the dissociation of FoxO1 from 14-3-3 proteins.
• Oxidative stress upregulated FoxO1 expression via JNK-mediated self-regulation.

Conclusions:

• The JNK/FoxO1 pathway is a key regulator of oxidative stress-induced apoptosis in MGCs.
• This pathway involves JNK-mediated FoxO1 nuclear translocation and altered protein interactions.
• Findings elucidate a novel mechanism in cellular response to oxidative damage.