Divergent roles of sirtuin 1 in human granulosa-lutein cells: similarities to human chorionic gonadotropin

Meidan, Rina; Szymańska, Magdalena

doi:10.1093/biolre/ioad026

Cited by 2 publications

(2 citation statements)

References 126 publications

(243 reference statements)

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“…In addition, SRT2104 was to inhibit endothelin-2 (EDN2) 144 . Based on the mutual regulatory interactions between SIRT1 and the cAMP signaling pathway, it is reasonable to attribute the similar effects of SRT2104 and hCG on ovulation and angiogenesis-related genes to elevated intracellular cAMP levels 145 .…”

Section: Srt2104 In Female Reproductive System Diseasesmentioning

confidence: 99%

Emerging roles of SIRT1 activator, SRT2104, in disease treatment

Chang,

Li,

Lin

et al. 2024

Sci Rep

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Silent information regulator 1 (SIRT1) is a NAD+-dependent class III deacetylase that plays important roles in the pathogenesis of numerous diseases, positioning it as a prime candidate for therapeutic intervention. Among its modulators, SRT2104 emerges as the most specific small molecule activator of SIRT1, currently advancing into the clinical translation phase. The primary objective of this review is to evaluate the emerging roles of SRT2104, and to explore its potential as a therapeutic agent in various diseases. In the present review, we systematically summarized the findings from an extensive array of literature sources including the progress of its application in disease treatment and its potential molecular mechanisms by reviewing the literature published in databases such as PubMed, Web of Science, and the World Health Organization International Clinical Trials Registry Platform. We focuses on the strides made in employing SRT2104 for disease treatment, elucidating its potential molecular underpinnings based on preclinical and clinical research data. The findings reveal that SRT2104, as a potent SIRT1 activator, holds considerable therapeutic potential, particularly in modulating metabolic and longevity-related pathways. This review establishes SRT2104 as a leading SIRT1 activator with significant therapeutic promise.

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Section: Srt2104 In Female Reproductive System Diseasesmentioning

confidence: 99%

Emerging roles of SIRT1 activator, SRT2104, in disease treatment

Chang,

Li,

Lin

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Sirtuin 1 (SIRT1) is an NAD-dependent deacetylase known as an antiageing factor. SIRT1 plays a pivotal role in regulating various physiological functions, including the cell cycle, DNA damage response, energy metabolism, cell ageing, and apoptosis [22,23]. The SIRT1 protein can modulate cell proliferation or apoptosis by deacetylating downstream substrates such as p53 and FOXO1 [24,25].…”

Section: Introductionmentioning

confidence: 99%

Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway

Liu,

Wang,

Yang

et al. 2024

Stem Cell Res Ther

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Background DNA damage and oxidative stress induced by chemotherapy are important factors in the onset of premature ovarian insufficiency (POI). Studies have shown that mitochondria derived from mesenchymal stem cells (MSC-Mito) are beneficial for age-related diseases, but their efficacy alone is limited. Pyrroloquinoline quinone (PQQ) is a potent antioxidant with significant antiaging and fertility enhancement effects. This study aimed to investigate the therapeutic effect of MSC-Mito in combination with PQQ on POI and the underlying mechanisms involved. Methods A POI animal model was established in C57BL/6J mice by cyclophosphamide and busulfan. The effects of MSC-Mito and PQQ administration on the estrous cycle, ovarian pathological damage, sex hormone secretion, and oxidative stress in mice were evaluated using methods such as vaginal smears and ELISAs. Western blotting and immunohistochemistry were used to assess the expression of SIRT1, PGC-1α, and ATM/p53 pathway proteins in ovarian tissues. A cell model was constructed using KGN cells treated with phosphoramide mustard to investigate DNA damage and apoptosis through comet assays and flow cytometry. SIRT1 siRNA was transfected into KGN cells to further explore the role of the SIRT1/ATM/p53 pathway in combination therapy with MSC-Mito and PQQ for POI. Results The combined treatment of MSC-Mito and PQQ significantly restored ovarian function and antioxidant capacity in mice with POI. This treatment also reduced the loss of follicles at various stages, improving the disrupted estrous cycle. In vitro experiments demonstrated that PQQ facilitated the proliferation of MitoTracker-labelled MSC-Mito, synergistically restoring mitochondrial function and inhibiting oxidative stress in combination with MSC-Mito. Both in vivo and in vitro, the combination of MSC-Mito and PQQ increased mitochondrial biogenesis mediated by SIRT1 and PGC-1α while inhibiting the activation of ATM and p53, consequently reducing DNA damage-mediated cell apoptosis. Furthermore, pretreatment of KGN cells with SIRT1 siRNA reversed nearly all the aforementioned changes induced by the combined treatment. Conclusions Our research findings indicate that PQQ facilitates MSC-Mito proliferation and, in combination with MSC-Mito, ameliorates chemotherapy-induced POI through the SIRT1/ATM/p53 signaling pathway.

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Divergent roles of sirtuin 1 in human granulosa-lutein cells: similarities to human chorionic gonadotropin

Cited by 2 publications

References 126 publications

Emerging roles of SIRT1 activator, SRT2104, in disease treatment

Emerging roles of SIRT1 activator, SRT2104, in disease treatment

Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway

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