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At least 217 records · Page 12Linked to original sources
PubMed2003

Monitoring changes in anthocyanin and steroid alkaloid glycoside content in lines of transgenic potato plants using liquid chromatography/mass spectrometry.

Transgenic potato plants overexpressing and repressing enzymes of flavonoids biosynthesis were created and analyzed. The selected plants clearly showed the expected changes in anthocyanins synthesis level. Overexpression of a DNA encoding dihydroflavonol 4-reductase (DFR) in sense orientation resulted in an increase in tuber anthocyanins, a 4-fold increase in petunidin and pelargonidin derivatives. A significant decrease in anthocyanin level was observed when the plant was transformed with a corresponding antisense construct. The transformation of potato plants was also accompanied by significant changes in steroid alkaloid glycosides (SAG) level in transgenic potato tuber. The changes in SAGs content was not dependent on flavonoid composition in transgenic potato. However, in an extreme situation where the highest (DFR11) or the lowest (DFRa3) anthocyanin level was detected the positive correlation with steroid alkaloid content was clearly visible. It is suggested that the changes in SAGs content resulted from chromatin stressed upon transformation. A liquid chromatography/mass spectrometry (LC/MS) system with electrospray ionization was applied for profiling qualitative and quantitative changes of steroid alkaloid glycosides in tubers of twelve lines of transgenic potato plants. Except alpha-chaconine and alpha-solanine, in the extracts from dried tuber skin alpha-solamargine and alpha-solasonine, triglycosides of solasonine, were identified in minor amounts, triglycosides of solanidine dehydrodimers were also recognized.

Alcohol Oxidoreductases↗
PubMed1967

Pool sizes of metabolic intermediates and their relation to glucose repression of beta-galactosidase synthesis in Escherichia coli.

1. The intermediary metabolism of two strains of Escherichia coli has been examined. One strain (Q22) exhibits acute transient repression of beta-galactosidase synthesis when glucose is supplied to cells growing on glycerol; the other strain (W3110) does not. The two strains do not differ genetically in their lac operons. 2. Strain Q22 uses about twice as much glucose as strain W3110 per unit of cell mass produced. 3. Pentose phosphate-cycle activity in the presence of glucose is much stronger in strain Q22 than in strain W3110. 4. In strain Q22 the pool sizes of glucose 6-phosphate, 6-phosphogluconate, fructose 1,6-diphosphate and NADPH increase when glucose is added to cells growing on glycerol, and beta-galactosidase synthesis is severely inhibited. After about 1hr. the synthesis of beta-galactosidase is partly resumed, and the pool sizes of the four compounds fall. ATP, NADH and several other phosphorylated compounds show no concentration changes. 5. These concentration changes do not occur in strain W3110, in which beta-galactosidase synthesis is only rather weakly repressed by glucose. 6. It is suggested that repression of enzyme synthesis by glucose requires the rapid operation of the pentose phosphate cycle, and is mediated by one of the four substances whose concentration rises and later falls in strain Q22. A definite choice of effector from among these four possibilities cannot at present be made.

Adenosine Triphosphate↗
PubMed2006

The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks.

NRs (nuclear receptors) regulate the expression of specific gene networks in target cells by recruiting cofactor complexes involved in chromatin remodelling and in the assembly of transcription complexes. The importance of activating gene expression, in metabolic tissues, is well established, but the contribution of transcriptional inhibition is less well defined. In this review, we highlight a crucial role for RIP140 (receptor-interacting protein 140), a transcriptional co-repressor for NR, in the regulation of metabolic gene expression. Many genes involved in lipid and carbohydrate metabolism are repressed by RIP140 in adipose and muscle. The repressive function of RIP140 results from its ability to bridge NRs to repressive enzyme complexes that modify DNA and histones. In the absence of RIP140, expression from many metabolic genes is increased so that mice exhibit a lean phenotype and resistance to high-fat-diet-induced obesity and display increased glucose tolerance and insulin sensitivity. We propose that a functional interplay between transcriptional activators and the co-repressor RIP140 is an essential process in metabolic regulation.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice.

The rodent liver displays marked age- and sex-dependent changes in androgen sensitivity due to the sexually dimorphic and temporally programmed expression of the androgen receptor (AR) gene. We have altered this normal phenotype by constitutive overexpression of the rat AR transgene in the mouse liver by targeting it via the human phenylalanine hydroxylase (hPAH) gene promoter. These transgenic animals in their heterozygous state produce an approximately 30-fold higher level of the AR in the liver as compared with the nontransgenic control. Androgen inactivation via sulfonation of the hormone by dehydroepiandrosterone sulfotransferase (DST), an androgen-repressible enzyme, also contributes to the age- and sex-dependent regulation of hepatic androgen sensitivity. DST has a broad range of substrate specificity and is responsible for the age- and sex-specific activation of certain polycyclic aromatic hepatocarcinogens as well, by converting them to electrophilic sulfonated derivatives. In the transgenic female, the hepatic expression of DST was approximately 4-fold lower than in normal females, a level comparable to that in normal males. The hPAH-AR mice will serve as a valuable model for studying the sex- and age-invariant expression of liver-specific genes, particularly those involved in the activation of environmental hepatocarcinogens such as the aromatic hydrocarbons.

Animals↗
PubMed1999

Yeast HOS3 forms a novel trichostatin A-insensitive homodimer with intrinsic histone deacetylase activity.

Histone deacetylases such as human HDAC1 and yeast RPD3 are trichostatin A (TSA)-sensitive enzymes that are members of large, multiprotein complexes. These contain specialized subunits that help target the catalytic protein to histones at the appropriate DNA regulatory element, where the enzyme represses transcription. To date, no deacetylase catalytic subunits have been shown to have intrinsic activity, suggesting that noncatalytic subunits of the deacetylase complex are required for their enzymatic function. In this paper we describe a novel yeast histone deacetylase HOS3 that is relatively insensitive to the histone deacetylase inhibitor TSA, forms a homodimer when expressed ectopically both in yeast and Escherichia coli, and has intrinsic activity when produced in the bacterium. Most HOS3 protein can be found associated with a larger complex in partially purified yeast nuclear extracts, arguing that the HOS3 homodimer may be dissociated from a very large nuclear structure during purification. We also demonstrate, using a combination of mass spectrometry, tandem mass spectrometry, and proteolytic digestion, that recombinant HOS3 has a distinct specificity in vitro for histone H4 sites K5 and K8, H3 sites K14 and K23, H2A site K7, and H2B site K11. We propose that while factors that interact with HOS3 may sequester the catalytic subunit at specific cellular sites, they are not required for HOS3 histone deacetylase activity.

Amino Acid Sequence↗
PubMed2002

Probiotics as modulators of the gut flora.

Probiotic ingestion can be recommended as a preventative approach to maintaining the balance of the intestinal microflora and thereby enhance 'well-being'. Research into the use of probiotic intervention in specific illnesses and disorders has identified certain patient populations that may benefit from the approach. Undoubtedly, probiotics will vary in their efficacy and it may not be the case that the same results occur with all species. Those that prove most efficient will likely be strains that are robust enough to survive the harsh physico-chemical conditions present in the gastrointestinal tract. This includes gastric acid, bile secretions and competition with the resident microflora. A survey of the literature indicates positive results in over fifty human trials, with prevention/treatment of infections the most frequently reported output. In theory, increased levels of probiotics may induce a 'barrier' influence against common pathogens. Mechanisms of effect are likely to include the excretion of acids (lactate, acetate), competition for nutrients and gut receptor sites, immunomodulation and the formation of specific antimicrobial agents. As such, persons susceptible to diarrhoeal infections may benefit greatly from probiotic intake. On a more chronic basis, it has been suggested that some probiotics can help maintain remission in the inflammatory conditions, ulcerative colitis and pouchitis. They have also been suggested to repress enzymes responsible for genotoxin formation. Moreover, studies have suggested that probiotics are as effective as anti-spasmodic drugs in the alleviation of irritable bowel syndrome. The approach of modulating the gut flora for improved health has much relevance for the management of those with acute and chronic gut disorders. Other target groups could include those susceptible to nosocomial infections, as well as the elderly, who have an altered microflora, with a decreased number of beneficial microbial species. For the future, it is imperative that mechanistic interactions involved in probiotic supplementation be identified. Moreover, the survival issues associated with their establishment in the competitive gut ecosystem should be addressed. Here, the use of prebiotics in association with useful probiotics may be a worthwhile approach. A prebiotic is a dietary carbohydrate selectively metabolised by probiotics. Combinations of probiotics and prebiotics are known as synbiotics.

Animals↗