Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia

Lee, Jia; Yang, Wei

doi:10.1007/s10142-023-01077-1

Cited by 6 publications

(2 citation statements)

References 53 publications

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“…A previous study suggested that Dox treatment induces an acute amplification of p300 level [ 48 ]. In addition, Dox treatment reduces the expression of histone deacetylases, such as HDAC2 [ 16 ], which contributes to the removal of H3K27ac [ 49 ]. These findings further support our discovery of increased H3K27ac levels following Dox treatment.…”

Section: Discussionmentioning

confidence: 99%

H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes

Hong,

Li,

et al. 2024

Clin Epigenet

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Background Doxorubicin (Dox) is an effective chemotherapeutic drug for various cancers, but its clinical application is limited by severe cardiotoxicity. Dox treatment can transcriptionally activate multiple cardiotoxicity-associated genes in cardiomyocytes, the mechanisms underlying this global gene activation remain poorly understood. Methods and results Herein, we integrated data from animal models, CUT&Tag and RNA-seq after Dox treatment, and discovered that the level of H3K27ac (a histone modification associated with gene activation) significantly increased in cardiomyocytes following Dox treatment. C646, an inhibitor of histone acetyltransferase, reversed Dox-induced H3K27ac accumulation in cardiomyocytes, which subsequently prevented the increase of Dox-induced DNA damage and apoptosis. Furthermore, C646 alleviated cardiac dysfunction in Dox-treated mice by restoring ejection fraction and reversing fractional shortening percentages. Additionally, Dox treatment increased H3K27ac deposition at the promoters of multiple cardiotoxic genes including Bax, Fas and Bnip3, resulting in their up-regulation. Moreover, the deposition of H3K27ac at cardiotoxicity-related genes exhibited a broad feature across the genome. Based on the deposition of H3K27ac and mRNA expression levels, several potential genes that might contribute to Dox-induced cardiotoxicity were predicted. Finally, the up-regulation of H3K27ac-regulated cardiotoxic genes upon Dox treatment is conservative across species. Conclusions Taken together, Dox-induced epigenetic modification, specifically H3K27ac, acts as a molecular switch for the activation of robust cardiotoxicity-related genes, leading to cardiomyocyte death and cardiac dysfunction. These findings provide new insights into the relationship between Dox-induced cardiotoxicity and epigenetic regulation, and identify H3K27ac as a potential target for the prevention and treatment of Dox-induced cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes

Hong,

Li,

et al. 2024

Clin Epigenet

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“…Cell apoptosis is a programmed cell death process characterized by the rupture of cell membranes and the subsequent release of inflammatory contents. [ 6 , 16 ] The primary objective of this study is to delve into the mechanisms underlying trophoblast cell apoptosis within the context of genital tract infections, particularly in relation to preterm PROM.…”

Section: Discussionmentioning

confidence: 99%

Exploratory study on the mechanism of necrotic effect of nourishing cells in the context of genital tract infection in premature rupture of membranes

Qian,

et al. 2023

Medicine

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To explore the mechanism of necrotic effect of nourishing cells in the context of genital tract infection in premature rupture of membranes (PROM). One hundred eight patients with PROM treated at our hospital from June 2020 to June 2022 were selected as the PROM group. Simultaneously, 108 cases of normal full-term pregnant women were chosen as the control group. Western blot analysis was performed to measure the relative expression levels of cysteinyl aspartate specific proteinase-1 (Caspase-1), cysteinyl aspartate specific proteinase-3 (Caspase-3), nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and interleukin (IL)-1β proteins, which are associated with necrosis of placental nourishing cells, in the placenta of both groups. TUNEL staining was used to detect the number of apoptotic placental nourishing cells. The differences in necrotic factors of placental nourishing cells were analyzed between full-term and preterm cases in the PROM group, as well as among patients with different genital tract infections. The apoptotic count of placental nourishing cells in the PROM group was 58.46 ± 11.26 cells/field, which was markedly higher than that of the control group (P < .05). The relative expression levels of the necrotic factors Caspase-1, Caspase-3, NLRP3, and IL-1β proteins in placental nourishing cells of the PROM group were 1.32 ± 0.26, 1.19 ± 0.30, 1.29 ± 0.28, and 1.23 ± 0.24, respectively. These values were significantly higher than those of the control group (P < .05). The relative expression levels of the necrotic factors Caspase-1, Caspase-3, NLRP3, and IL-1β proteins in placental nourishing cells were compared between full-term and preterm patients in the PROM group (P > .05). The relative expression levels of the necrotic factors Caspase-1, Caspase-3, NLRP3, and IL-1β proteins in placental nourishing cells were higher in patients with multiple genital tract infections compared to those with single infections or no infections in the PROM group (P < .05). PROM is associated with a significant upregulation of placental nourishing cell apoptosis and necrotic factors, including Caspase-1, Caspase-3, NLRP3, and IL-1β proteins. This upregulation is correlated with the presence of genital tract infections.

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The crosstalk between cell death and pregnancy related diseases: A narrative review

Xie,

Liu,

Gao

et al. 2024

Biomedicine & Pharmacotherapy

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Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia

Cited by 6 publications

References 53 publications

H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes

H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes

Exploratory study on the mechanism of necrotic effect of nourishing cells in the context of genital tract infection in premature rupture of membranes

The crosstalk between cell death and pregnancy related diseases: A narrative review

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