The protective effect of sulforaphane against oxidative stress in granulosa cells of patients with polycystic ovary syndrome (PCOS) through activation of AMPK/AKT/NRF2 signaling pathway

Taheri, Maryam; Roudbari, Nasim Hayati; Amidi, Fardin; Parivar, Kazem

doi:10.1016/j.repbio.2021.100563

Cited by 17 publications

(16 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oxidative stress leads to the abnormal accumulation of ROS, which is commonly caused by an imbalance between pro-oxidants and antioxidants [ 6 ]. Excessive oxidative stress in ovarian granulosa cells leads to apoptosis [ 36 , 37 ]. Several studies have reported the accumulation of oxidative circulating markers in patients with PCOS and have been considered as potential inducers of PCOS pathogenesis [ 3 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT/ERK signalling pathway

et al. 2023

View full text Add to dashboard Cite

Background The development of polycystic ovary syndrome (PCOS) is closely correlated with apoptosis and oxidative stress in ovarian granulosa cells. Kisspeptin plays an important role in reproductive organ function. This study aimed to explore the role of kisspeptin in PCOS and oxidative stress-triggered apoptosis of ovarian granular cells. Methods A PCOS rat model was established by injecting dehydroepiandrosterone (DHEA) and feeding the rats a high-fat diet. The RNA and protein levels of kisspeptin were analysed by quantitative PCR, western blotting, and histological staining. Tissue damage was evaluated using haematoxylin and eosin (H&E) staining. The viability and proliferation of human granulosa cell KGN were measured using the cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays. Cell cycle and apoptosis were analysed by flow cytometry. Oxidative stress was analysed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels. Results Kisspeptin was downregulated in the ovarian granulosa cells of PCOS rats compared to those of control rats. Kisspeptin overexpression enhanced KGN cell proliferation and inhibited apoptosis. ROS generation was suppressed by kisspeptin, along with decreased levels of MDA and increased levels of the antioxidants GSH, SOD, and CAT. Kisspeptin activates PI3K/AKT and ERK signalling, and inactivation of ERK1/2 suppresses the protective role of kisspeptin in ovarian granulosa cells. Conclusion Kisspeptin improves proliferation and alleviates apoptosis and oxidative stress in ovarian granulosa cells by activating PI3K/AKT and ERK signalling.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT/ERK signalling pathway

et al. 2023

View full text Add to dashboard Cite

show abstract

“…42,43 Nrf2 binds to the antioxidant response element (ARE) in the promoter region of the antioxidant enzyme gene, induces its expression, and ultimately promotes the antioxidant defense system, which is an essential molecule in redox system. 44 Studies have proved that activation of AMPK reduced the level of Nrf2 in cells and induced apoptosis of pancreatic cancer cells. 45 Gao et al reported that cordycepin enhanced the chemical sensitivity of ESCC cells to DDP by inducing AMPK activation and inhibiting the AKT signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Nrf2 is an important transcription factor in that regulates cellular oxidative stress 42,43 . Nrf2 binds to the antioxidant response element (ARE) in the promoter region of the antioxidant enzyme gene, induces its expression, and ultimately promotes the antioxidant defense system, which is an essential molecule in redox system 44 . Studies have proved that activation of AMPK reduced the level of Nrf2 in cells and induced apoptosis of pancreatic cancer cells 45 .…”

Section: Discussionmentioning

confidence: 99%

CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas

Fang

et al. 2022

Molecular Carcinogenesis

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is a common human malignancy characterized by late-stage diagnosis, metastasis, and poor prognosis. Cisplatin (DDP)-based chemotherapy has been the most predominant treatment for patients with ESCC. However, the high rate of DDP resistance and toxicity seriously hinder its clinical application. Then, the optimized strategy and mechanisms for ESCC to enhance DDP sensitivity are in great demand. Accumulating evidence have shown that chaperone proteins are closely related to the tumorigenesis and drug resistance of cancers. Chaperonin containing TCP1 complex 4 (CCT4) is a recent identified member of the family. However, its expression and function in ESCC have not been well illustrated. In this study, we found that CCT4 was highly expressed in human ESCC tissues and cell lines, and closely related to the poor prognosis. Moreover, CCT4 silence raised oxidative stress and inhibited glycolysis of ESCC cells, which significantly inhibited cell proliferation and migration, promoted apoptosis and caused cell cycle arrest in ESCC cells. Interestingly, CCT4 knockdown enhanced the sensitivity of KYSE150 cells to DDP by regulating AMPK/AKT/Nrf2 signaling pathway and inhibiting glycolysis ability. Taken together, our results indicate that targeting CCT4 may be a therapeutic target in ESCC patients, which provides a theoretical basis to enhance the sensitivity of DDP in ESCC.

show abstract

“…The transporter-dependent pathway activated ferroptosis by inhibiting SLC7A11 ( 16 ). As we know, oxidative stress and oxidative stress-induced cell death in GCs are associated with the pathogenesis of PCOS ( 9 , 17 ). However, whether oxidative stress-mediated GC ferroptosis is involved in the development of PCOS is still unclear.…”

Section: Introductionmentioning

confidence: 99%

NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation

Tang

Jiang

Hua

et al. 2023

Endocrine Connections

View full text Add to dashboard Cite

Background: Polycystic ovary syndrome (PCOS) is an androgen disorder and ovarian dysfunction disease in women of reproductive age. The cell death of granulosa cells plays an important role in the development of PCOS. However, the mechanism of granulosa cell death is still unclear. Methods: In the current study, NEDD4L was found to be elevated in PCOS GEO databases and mouse models. The cell viability was analyzed by CCK-8 and FDA staining. The expression of ferroptosis markers was assessed by Elisa and immunofluorescence. The direct interaction of GPX4 and NEDD4L was verified by CO-IP assay. Result: Functionally, results from CCK-8 and FDA staining demonstrated that NEDD4L inhibited the cell viability of KGN cells and NEDD4L increased the levels of iron, malonyldialdehyde (MDA), reactive oxygen species (ROS), and decreased glutathione (GSH) levels. Moreover, the cell death of KGN induced by NEDD4L was blocked by ferroptosis inhibitor, suggesting that NEDD4L regulates KGN cell ferroptosis. Mechanistically, NEDD4L directly interacts with GPX4 and promotes GPX4 ubiquitination and degradation. Conclusion: Taken together, our study indicated that NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation and contributes to the development of PCOS.

show abstract

The protective effect of sulforaphane against oxidative stress in granulosa cells of patients with polycystic ovary syndrome (PCOS) through activation of AMPK/AKT/NRF2 signaling pathway

Cited by 17 publications

References 41 publications

Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT/ERK signalling pathway

Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT/ERK signalling pathway

CCT4 knockdown enhances the sensitivity of cisplatin by inhibiting glycolysis in human esophageal squamous cell carcinomas

NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation

Contact Info

Product

Resources

About