RESUMO
Oleate induces the transcription of genes involved in peroxisome biogenesis and stimulates the proliferation of these organelles in Saccharomyces cerevisiae. Previously, we have reported the identification of a region containing a positive regulatory element in the 5' flanking region of the FOX3 gene encoding the peroxisomal enzyme 3-oxoacyl-CoA thiolase. This region contains a 23-bp imperfect inverted-repeat sequence. Full induction, in response to oleate, is mediated by the intact dyad. However, one half-site of the inverted repeat is also able to mediate induction of transcription in response to oleate, albeit to a small extent. Furthermore, the weak binding of protein to each part of the inverted repeat proved to be correlated with the weak activation of transcription, in support of oleate. A DNase-I footprint covered the entire dyad and DNA band-shift experiments indicated that one or more trans-acting factors bind to the imperfect palindrome. The binding of protein to this element seems to be correlated with transcriptional activation, since mutations in both halves of the inverted dyad affected both transcriptional activation and protein binding in vitro. Similar oleate-responsive elements are commonly found in the 5' flanking regions of genes encoding proteins involved in peroxisome biogenesis and the factor(s) binding to oleate-responsive element(s) could therefore be involved in coordination of the expression of oleate-inducible genes and the proliferation of peroxisomes.
Assuntos
Acetil-CoA C-Aciltransferase/genética , Microcorpos/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Sequências Reguladoras de Ácido Nucleico , Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Acetil-CoA C-Aciltransferase/biossíntese , Sequência de Bases , DNA Fúngico/genética , DNA Fúngico/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Microcorpos/enzimologia , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ácido Oleico , Ligação Proteica , Sequências Repetitivas de Ácido Nucleico , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura , Transcrição Gênica/efeitos dos fármacosRESUMO
The earlier described age-related decreases in vasopressin innervation of extra-hypothalamic rat brain regions were found to coincide with a decrease in vasopressin expression in the cells where these fibers originated. A significant age-related decrease in the number of vasopressin-immunoreactive cell bodies was found in the medial amygdala and locus coeruleus of senescent Brown-Norway (BN/BiRij) rats (33 months) when compared to middle-aged (19 months) and young (3 months) rats. In addition, total testosterone plasma levels were significantly reduced in middle-aged and old rats as compared to young animals and the number of vasopressin-immunoreactive cells in both the medial amygdala and locus coeruleus correlated significantly with the decreased testosterone levels in a similar way as found earlier for vasopressin terminals.
