Epigenetic studies in insects and the valproic acid perspective

Santos, D S; Rocha, Marina Amorim; Mello, Maria Luiza S.

doi:10.1590/1519-6984.256045

Cited by 3 publications

(3 citation statements)

References 89 publications

(120 reference statements)

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“…The molecular mechanisms responsible for ethnic differences in VPA metabolism are explained by advances in molecular biology and population genetic studies in recent years [61,62]. In particular, significant differences in the population frequency of some variative ("mutant" or minor) SNVs in different countries of the world have been shown, which cause differences in the prevalence of patients with neurological diseases and mental disorders who are homozygous and heterozygous for the minor allele(s) of the gene(s) of the CYP family and associated with the impaired P-oxidation of VPA in the liver and the development of ADRs [63][64][65][66][67][68] (Table 2).…”

Section: Valproic Acid P-oxidation and Ethnicitymentioning

confidence: 99%

Ethnic Aspects of Valproic Acid P-Oxidation

Shnayder,

Grechkina,

Trefilova

et al. 2024

Biomedicines

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The safety of the use of psychotropic drugs, widely used in neurological and psychiatric practice, is an urgent problem in personalized medicine. This narrative review demonstrated the variability in allelic frequencies of low-functioning and non-functional single nucleotide variants in genes encoding key isoenzymes of valproic acid β-oxidation in the liver across different ethnic/racial groups. The sensitivity and specificity of pharmacogenetic testing panels for predicting the rate of metabolism of valproic acid by P-oxidation can be increased by prioritizing the inclusion of the most common risk allele characteristic of a particular population (country).

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Section: Valproic Acid P-oxidation and Ethnicitymentioning

confidence: 99%

Ethnic Aspects of Valproic Acid P-Oxidation

Shnayder,

Grechkina,

Trefilova

et al. 2024

Biomedicines

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“…Insects have been suggested as an alternative model for research on epigenetic effects promoted by VPA, because of their shorter generation intervals, the opportunity for analyzing larger samples, and diminished ethical concerns compared with those for the experimental use of mammals. Therefore, T. infestans may be considered an attractive candidate for evaluating pathway mechanisms underlying VPA action [ 78 ].…”

Section: Response To Epigenetic Modulatorsmentioning

confidence: 99%

“…In the presence of VPA, T. infestans cells revealed unexpected results [ 52 , 78 , 79 ]. One-hour following the abdominal injection of a 0.05 mM VPA solution in T. infestans nymphs or after a 4-h in vitro culture of the Malpighian tubules of this insect in the presence of 0.05–0.5 mM VPA, unpacking of the chromocenter was demonstrated in a portion of the Malpighian tubule cells ( Figure 4 g) [ 52 , 79 ].…”

Section: Response To Epigenetic Modulatorsmentioning

confidence: 99%

Nuclear Morphofunctional Organization and Epigenetic Characteristics in Somatic Cells of T. infestans (Klug, 1834)

Mello

2023

Pathogens

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Triatoma infestans (Klug) is an insect recognized as not only an important vector of South American trypanosomiasis (Chagas disease) but also a model of specific cellular morphofunctional organization and epigenetic characteristics. The purpose of the present review is to highlight certain cellular processes that are particularly unveiled in T. infestans, such as the following: (1) somatic polyploidy involving nuclear and cell fusions that generate giant nuclei; (2) diversification of nuclear phenotypes in the Malpighian tubules during insect development; (3) heterochromatin compartmentalization into large bodies with specific spatial distribution and presumed mobility in the cell nuclei; (4) chromatin remodeling and co-occurrence of necrosis and apoptosis in the Malpighian tubules under stress conditions; (5) epigenetic markers; and (6) response of heterochromatin to valproic acid, an epidrug that inhibits histone deacetylases and induces DNA demethylation in other cell systems. These cellular processes and epigenetic characteristics emphasize the role of T. infestans as an attractive model for cellular research. A limitation of these studies is the availability of insect supply by accredited insectaries. For studies that require the injection of drugs, the operator’s dexterity to perform insect manipulation is necessary, especially if young nymphs are used. For studies involving in vitro cultivation of insect organs, the culture medium should be carefully selected to avoid inconsistent results.

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Exploration of DNA methylation in the chromatin of <i>Triatoma infestans</i> (Klug)

dos Anjos,

Rocha,

Vidal

et al. 2023

CYTOLOGIA

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Sodium valproate (VPA) is an epidrug that inhibits histone deacetylases and favors histone acetylation and DNA demethylation, thereby inducing chromatin remodeling in several cell types. Although VPA induced heterochromatin decondensation in the hemipteran Triatoma infestans, this phenomenon was not favored by histone acetylation. Considering that DNA demethylation leading to chromatin unpacking is another consequence of VPA action in several organisms, we used immunofluorescence to investigate whether cytosine methylation was the target of VPA action that affected heterochromatin remodeling in T. infestans. In addition, Fourier transform infrared (FTIR) analysis was used to evaluate the participation of cytosine in T. infestans DNA. Immunofluorescence results indicated the absence of 5-methylcytosine signals in heterochromatin, but the presence of these signals in euchromatin, where demethylation was promoted by VPA. The FTIR spectra of T. infestans global DNA exhibited marks indicative of AT richness and a low representation of cytosine contribution. In conclusion, the chromatin remodeling event previously reported in the heterochromatin compartment of T. infestans in response to VPA, which was not due to histone acetylation, was also not due to DNA cytosine demethylation.

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Epigenetic studies in insects and the valproic acid perspective

Cited by 3 publications

References 89 publications

Ethnic Aspects of Valproic Acid P-Oxidation

Ethnic Aspects of Valproic Acid P-Oxidation

Nuclear Morphofunctional Organization and Epigenetic Characteristics in Somatic Cells of T. infestans (Klug, 1834)

Exploration of DNA methylation in the chromatin of <i>Triatoma infestans</i> (Klug)

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