Subcellular distribution and Nrf2/Keap1-interacting properties of Glutathione S-transferase P in hepatocellular carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.Glutathione S-transferase P (GSTP) plays a key role in liver cancer by interacting with the Nrf2/Keap1 pathway. Inhibiting GSTP can lead to cancer cell death, suggesting a therapeutic target for hepatocellular carcinoma (HCC).
Area Of Science
- Biochemistry
- Molecular Biology
- Oncology
Background
- Glutathione S-transferase P (GSTP) is an oncogene and drug-metabolizing enzyme involved in liver carcinogenesis.
- GSTP acts as a chaperone for signaling proteins and influences cellular redox balance.
- Its role in hepatocellular carcinoma (HCC) and interaction with key transcription factors warrants investigation.
Purpose Of The Study
- To explore the role of GSTP in HCC by examining its interaction with nuclear factor erythroid 2-related factor 2 (Nrf2).
- To investigate the expression, cellular distribution, and glutathionylation function of the GSTP1-1 isoform in HCC.
- To elucidate the physical and functional interplay between GSTP, Nrf2, and Keap1 in liver cancer development.
Main Methods
- Utilized a mouse model of N-nitrosodiethylamine (DEN)-induced HCC and human HCC cell lines (HepG2, Huh-7).
- Employed immunoprecipitation and gene manipulation techniques to study protein interactions.
- Assessed protein expression, enzymatic activity, cellular localization, and protein glutathionylation (PSSG).
Main Results
- GSTP expression, activity, and nuclear levels increased during DEN-induced HCC development in mice, with elevated PSSG in tumors.
- HCC cells showed higher GSTP levels and nuclear localization compared to non-cancerous cells, alongside increased GSH and PSSG.
- GSTP inhibition induced apoptosis in HCC cells; GSTP transfection activated Nrf2 in non-cancerous cells, and GSTP co-immunoprecipitated with Nrf2 and Keap1.
Conclusions
- GSTP expression and localization are altered in HCC, contributing to redox reprogramming.
- GSTP influences the Nrf2/Keap1 transcriptional system, impacting HCC progression.
- GSTP emerges as a potential therapeutic target for hepatocellular carcinoma.
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