Biology subjects

Mello, M. L. S.

Publications and source records attributed to Mello, M. L. S..

4 recordsLinked to original sources

bioRxiv2026

Mitotic catastrophe and other cellular instability events in sodium valproate-treated HeLa cells

Valproic acid/sodium valproate (VPA) is a widely prescribed anticonvulsant and has also been used against certain tumor cells. It is a potent modulator of gene expression. Its ability to induce apoptosis has been well documented in HeLa cells. However, another form of cell death - mitotic catastrophe - has not yet been explored in VPA-treated HeLa cells. Here, we investigated the effects of VPA treatment on mitotic catastrophe characteristics, including morphological features and their frequencies, fluorescence intensity signals of caspase-2 and p53, and the expression and abundance of DNMT1 and DNMT3B. An increased frequency of mitotic catastrophe was observed not only morphologically, but also through enhanced induction of caspase-2, involvement of p53, at least under more drastic VPA treatment, but without a decrease in DNMT1 or DNMT3B levels. Additionally, enhancement of mitotic catastrophe coincided with a reduction in mitotic chromosome abnormalities. Increased DNMT3B expression following VPA action, may be favored by previously reported chromatin decondensation induced by this drug. Enhanced CpG methylation of specific DNA sites could thus be promoted. In conclusion, VPA was shown to trigger metabolic pathways linked to different forms of cell death in HeLa cells, supporting its oncosuppressive potential.

cell biology↗

bioRxiv2025

Nuclear phenotypic changes in cells originating from migrating tenocytes in tendon explants

Tenocytes migrating from cultured rat tendon explants aggregate and gradually align in parallel rows with the tendons long axis as the explant period extends up to 12 days and collagen bundles become structurally remodeled. Tendon architecture and mechanical load are known to affect fibroblast phenotypes; thus, we studied cell cultures derived from tenocytes at early and later migration stages using image analysis and immunofluorescence for selected epigenetic markers to identify differences in nuclear characteristics across migration periods. Feulgen-DNA amounts and global DNA 5-methylcytosine and acetylated H3K9 distribution were not found to differ in the cells originating from tenocytes that migrated at the 8- and 12-day periods of tendon culture. However, light absorbance, fractal dimension, and margination features related to chromatin condensation and distribution in the Feulgen-stained cell nuclei differed during these periods. Accumulation of the H3K4me2 marker at the nuclear periphery in cells obtained after a longer explant culture period, when the margination feature reaches larger values, may represent the acquisition of an enhanced transcriptional memory that could affect future gene expression levels. Further assays are required to determine whether the present image analysis results correlate with the differential potential of these cells for extracellular matrix synthesis and practical bioengineering purposes.

cell biology↗

bioRxiv2025

Sodium valproate induces chromatin remodeling in U-251MG glioblastoma cells

The development and progression of glioblastoma, the most aggressive malignant intracranial tumor with a poor prognosis, are influenced by mutations, the overexpression of oncogenes, and epigenetic factors, particularly those related to DNA methylation status and histone post-translational modifications. Valproic acid (VPA), a classic histone deacetylase (HDAC) inhibitor, has shown promise both on its own and in combination with other drugs as a therapeutic agent against various solid tumors, including gliomas. Given VPAs reported effects on chromatin supraorganization and expression activity in several cell types, we studied textural features that may indicate changes in chromatin structure in U-251MG glioblastoma cells cultured in the presence of VPA, utilizing image cytometry. For comparison, cells treated with 5-aza-CdR served as a positive control for DNA demethylation. Chromatin remodeling was observed in VPA-treated cells, which displayed decreased HDAC activity and increased histone H3 acetylation, whereas no such changes were detected in 5-aza-CdR-treated cells. These findings suggest that, despite the significance of DNA methylation alterations in glioblastoma cells, the chromatin remodeling observed through image cytometry in VPA-treated U-251MG cells is more closely associated with induced changes involving histone modifications rather than with DNA demethylation.

cell biology↗

bioRxiv2018

Valproic acid attenuates hyperglycemia-induced complement and coagulation cascade gene expression

Atherothrombosis remains the leading cause of morbidity and mortality in patients diagnosed with diabetes mellitus, but the molecular mechanisms underpinning this remain unresolved. As the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is an interest in understanding the mechanisms of hepatic cell activation under hyperglycemia and whether this can be attenuated pharmacologically. We have previously shown that hyperglycemia stimulates major changes in chromatin organisation and metabolism in hepatocytes, and that the histone deacetylase inhibitor valproic acid (VPA; IUPAC: 2-propylpentanoic acid) is able to reverse some of these metabolic changes. In this study, we used deep transcriptome sequencing to show that VPA attenuates hyperglycemia-induced activation of complement and coagulation cascade genes. These findings reveal a novel mechanism of VPA protection against hyperglycemia, which might improve the therapeutic approaches for diabetes.

molecular biology↗