47 research outputs found
Tumor cell uptake of the metastasis inhibitor ruthenium complex NAMI-A and its in vitro effects on KB cells
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Synthesis,characterization and antitumor activity of Platinum (II) complexes with diethyl and monoethyl 2-quinolylmethylphosphonates.
No full textIdentification of a novel Sp1 splice variant as a strong transcriptional activator
No full textThe transcription factor Sp1 regulates expression of numerous genes involved in many cellular processes.
Different post-transcriptional modifications can influence the transcriptional control activity and stability
of Sp1. In addition to these modifications, alternative splicing isoforms may also be the basis of its distinct
functional activities. In this study, we identified a novel alternative splice isoform of Sp1 named
Sp1c. This variant is generated by exclusion of a short domain, which we designate a, through alternative
splice acceptor site usage in the exon 3. The existence of this new isoform was confirmed in vivo by Western
blotting analysis. Although at very low levels, Sp1c is ubiquitously expressed, as seen in its fulllength
Sp1. A preliminary characterization of Sp1c shows that: (a) Sp1c works as stronger activator of
transcription than full-length Sp1; (b) percentage of HEK293 Sp1c-overexpressing cells is higher in G1
phase and lower in S phase than percentage of HEK293 Sp1-overexpressing cells
Statins, fibrates and retinoic acid upregulate mitochondrial acylcarnitine carrier gene expression
No full textIn this study, we investigated the effects of statins, fibrates, 9-cis-retinoic acid and forskolin on the transcription of the mitochondrial carnitine/acylcarnitine carrier (CAC) gene. Statins, fibrates, retinoic acid and forskolin activate luciferase gene reporter activity driven by the -334/+3 bp region of the human CAC promoter containing wild-type (but not mutated) PPRE. These four agents also increase CAC transcript and protein levels. The combinations of statins and fibrates, retinoic acid and fibrates and fibrates and forskolin act synergistically. Mevalonate abolishes the activation of CAC gene expression by statins; the inhibitor of the PKA pathway H89 suppresses the stimulation of CAC gene expression by forskolin. Because CAC is essential for fatty acid beta-oxidation, the above results on the regulation of CAC gene expression provide a novel contribution to the understanding of the hypolipidemic action of statins, fibrates and retinoic aci
Synthesis and biological properties of new α-methylene-γ-butyrolactones and α,β-unsaturated δ-lactones
No full textThe synthesis of a series of α-methylene-γ-butyrolactones (compounds 4a, 4b, 6–12, 16, 17) and α,β-unsaturated-δ-lactones (compounds 19−23, 25, 26) starting from 4,4-dimethyldihydrofuran-2,3-dione (1) has been described. Their chemical structures were assigned by spectroscopic evidence. These new compounds exhibited significantly different antiproliferative properties against cultured human tumor cell lines with their IC50 values ranging from 0.88 to > 20.00 μM
Mitochondrial pathways to autism
No full textAutism is a severe pervasive developmental disorder characterized by variable degrees of impairment in language, communication and social skills, as well as by repetitive and stereotypic patterns of behaviour. Despite strong familial components, clinical and genetic complexities have posed a major challenge to our understanding of autism pathogenesis. A significant subset of autistic patients display biochemical or neuropathological evidence of mitochondrial dysfunction and/or oxidative stress. However, only in a very few cases abnormal energy metabolism could be linked to a specific genetic defect. Interest in assessing the role of mitochondria in this disorder has been revitalized by the association between autism and variants of the SLC25A12 gene [1], which encodes the predominant isoform of the mitochondrial aspartate/glutamate carrier (AGC) in brain [2]. Cytosolic Ca2+ can rapidly activate AGC transport through four “EF-hand” domains located at its N-terminus, thereby increasing the NADH/NAD ratio in the mitochondrial matrix and consequently boosting electron flow through the respiratory chain and ATP generation by oxidative phosphorylation [3]. Post-mortem studies of temporocortical gray matter from matched patient–control pairs revealed that AGC transport rates were significantly higher in brains from autistic patients [4]. This difference was blunted by Ca2+ chelator EGTA and direct fluorimetric measurements confirmed significantly higher Ca2+ levels in the patients, compared to their matched controls [4]. Oxidized mitochondrial proteins were markedly increased in the majority of the patients tested. Interestingly, oxidative damage correlated with the reduction of complex I activity indicating that excessive Ca2+ levels boost AGC activity in neurons and, to a more variable degree, cause oxidative stress and mitochondrial dysfunction in autistic brains. Furthermore, we identified a protective SLC25A12 gene variant in a sizable group of unaffected siblings modulating AGC1 mRNA levels and protein activity. Our results suggest that mitochondria may play a critical role in the cascade of signalling events leading to autism and in determining to what extent different prenatal triggers will derange neurodevelopment and yield abnormal postnatal behaviour
Free exchange across cells,and echistatin-sensitive membrane target for the metastasis inhibitor NAMI-A(imidazolium trans-imidazole dimethyl sulfoxide tetrachlororuthenate)ON KB Tumor cells.
No full textPreliminary biological assay on cerebroside mixture from Euphorbia nicaeensis All.Isolation and structure determination of five glucocerebrosides.
No full textFive membered [C,N] and [N,O]metallocyclic compex of palladium(II) with monoalkyl[a-(4-benzeneazoanilino)-N-benzyl]phosphonates: synthesis, characterization and antitumor activity
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