Assuntos
Cegueira/epidemiologia , Doenças Cardiovasculares/epidemiologia , Pseudoxantoma Elástico/complicações , Pele/patologia , Adolescente , Adulto , Idoso , Cegueira/etiologia , Doenças Cardiovasculares/etiologia , Criança , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pseudoxantoma Elástico/diagnóstico , Pseudoxantoma Elástico/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
Multiple mechanisms regulate the expression of the tyrosine hydroxylase (Th) gene, which encodes the rate-limiting enzyme in the biosynthesis of catecholamines. Sodium butyrate (SOB), a physiological histone deacetylase (HDAC) inhibitor, was reported to stimulate the Th gene promoter activity in reporter gene assays. However, the expression of the endogenous Th gene in PC12 cells was reported to be either stimulated or inhibited by SOB. Here, we report that SOB and other HDAC inhibitors drastically (up to 90%) and reversibly decrease the level of TH mRNA in PC12 cells. We also show that SOB does not influence the transcription initiation rate of the Th gene but perturbs the formation of protein-RNA complexes at the 3'UTR of the gene. Our results suggest that SOB inhibits the expression of the Th gene by destabilizing TH mRNAs.
Assuntos
Butiratos/administração & dosagem , Inibidores de Histona Desacetilases , RNA Mensageiro/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Relação Dose-Resposta a Droga , Estabilidade Enzimática , Células PC12 , RatosRESUMO
We have examined the structure and function of Ca2+ channels in excitable endocrine cell types, in rat adrenal glomerulosa cells and in two insulin producing cell types, the rat pancreatic beta cell and the INS-1 cell line. In previous studies on glomerulosa cells, we observed low (T-type) and high threshold (L-type) voltage dependent Ca2+ currents in addition to a K+ induced inward rectifying Ca2+ current (Igl). beta cells are known to exhibit T-, L- and N-type currents. We have now found that INS-1 cells also show low threshold (T-type) and high threshold Ca2+ currents. The latter was further resolved by organic inhibitors into L-type and P/Q-type currents and no Igl was detected. The expression of the pore-forming alpha 1 subunit of voltage dependent Ca2+ channels was studied by means of reverse transcription-polymerase chain reaction (RT-PCR), followed by restriction enzyme mapping and/or sequencing. Both in glomerulosa and pancreatic beta cells, the neuroendocrine (D) class of the alpha 1 subunit, known to be responsible for L-type current, represents the majority of the PCR product. Comparable amounts of the neuroendocrine (D) and the neuronal A-type alpha 1 subunits dominate the message in INS-1 cells. Different characteristics of Ca2+ currents in these cell types is discussed in view of the channel repertoire.
