Chromatin Remodeling, Cell Proliferation and Cell Death in Valproic Acid-Treated HeLa Cells

Autor(es)

Felisbino, Marina Barreto ^[1] ; Tamashiro, Wirla M. S. C. ^[2] ; Mello, Maria Luiza S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas Unicamp, Inst Biol, Dept Struct & Physiol Biol, Sao Paulo - Brazil

^[2] Univ Campinas UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 6, n. 12 DEC 9 2011.
• Citações Web of Science: 20

Resumo

Background: Valproic acid (VPA) is a potent anticonvulsant that inhibits histone deacetylases. Because of this inhibitory action, we investigated whether VPA would affect chromatin supraorganization, mitotic indices and the frequency of chromosome abnormalities and cell death in HeLa cells. Methodology/Principal Findings: Image analysis was performed by scanning microspectrophotometry for cells cultivated for 24 h, treated with 0.05, 0.5 or 1.0 mM VPA for 1-24 h, and subjected to the Feulgen reaction. TSA-treated cells were used as a predictable positive control. DNA fragmentation was investigated with the TUNEL assay. Chromatin decondensation was demonstrated under TSA and all VPA treatments, but no changes in chromosome abnormalities, mitotic indices or morphologically identified cell death were found with the VPA treatment conditions mentioned above, although decreased mitotic indices were detected under higher VPA concentration and longer exposure time. The frequency of DNA fragmentation identified with the TUNEL assay in HeLa cells increased after a 24-h VPA treatment, although this fragmentation occurred much earlier after treatment with TSA. Conclusions/Significance: The inhibition of histone deacetylases by VPA induces chromatin remodeling in HeLa cells, which suggests an association to altered gene expression. Under VPA doses close to the therapeutic antiepileptic plasma range no changes in cell proliferation or chromosome abnormalities are elicited. The DNA fragmentation results indicate that a longer exposure to VPA or a higher VPA concentration is required for the induction of cell death. (AU)

• Processo FAPESP: 09/11763-0 - Textura cromatínica, anomalias cromossômicas e morte celular em condições de inibição de deacetilases de histonas em células HeLa e 3T3
• Beneficiário: Marina Barreto Felisbino
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 10/50015-6 - Estrutura e organização da cromatina com o envelhecimento e o diabetes frente a alterações induzidas em marcadores epigenéticos
• Beneficiário: Maria Luiza Silveira Mello
• Modalidade de apoio: Auxílio à Pesquisa - Temático