RESUMEN
A new indanone (1) has been isolated from the filamentous marine cyanobacterium Lyngbya majuscula, and its structure determined spectroscopically. Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis. Compound 1 inhibits hypoxia-induced activation of the VEGF gene promoter in Hep3B human liver tumor cells, in vitro.
Asunto(s)
Cianobacterias/química , Regulación de la Expresión Génica/efectos de los fármacos , Indanos/química , Hipoxia de la Célula , Factores de Crecimiento Endotelial/genética , Humanos , Indanos/aislamiento & purificación , Indanos/farmacología , Linfocinas/genética , Regiones Promotoras Genéticas , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The structure of apakaochtodene A, the minor isomer of two tetrahalogenated ochtodene monoterpenes, isolated from the red marine alga Portieria hornemannii (Lyngbye) Silva has been identified as 6(S)-bromo-1,4(S),8(R)-trichloro-2(Z)-ochtodene (1) by NMR spectral and X-ray crystallographic analysis. Its geometrical isomer, apakaochtodene B (2), which could not be separated from 1 and thus characterized as a 95:5 mixture of 2:1 had (1)H and (13)C NMR spectral characteristics similar to previously known ochtodene (3) and the related tetrahalogenated monoterpene 4.
Asunto(s)
Monoterpenos , Rhodophyta/química , Terpenos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Biología Marina , Estructura Molecular , Terpenos/químicaRESUMEN
A cause of aging in Saccharomyces cerevisiae is the accumulation of extrachromosomal ribosomal DNA circles (ERCs). Introduction of an ERC into young mother cells shortens life span and accelerates the onset of age-associated sterility. It is important to understand the process by which ERCs are generated. Here, we demonstrate that homologous recombination is necessary for ERC formation. rad52 mutant cells, defective in DNA repair through homologous recombination, do not accumulate ERCs with age, and mutations in other genes of the RAD52 class have varying effects on ERC formation. rad52 mutation leads to a progressive delocalization of Sir3p from telomeres to other nuclear sites with age and, surprisingly, shortens life span. We speculate that spontaneous DNA damage, perhaps double-strand breaks, causes lethality in mutants of the RAD52 class and may be an initial step of aging in wild-type cells.
Asunto(s)
Senescencia Celular/genética , Reparación del ADN/genética , ADN Circular/genética , ADN Ribosómico/genética , Saccharomyces cerevisiae/genética , Proteínas Reguladoras de Información Silente de Saccharomyces cerevisiae , Proteínas de Unión al ADN/genética , Epistasis Genética , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Proteínas Fúngicas/genética , Genotipo , Infertilidad/genética , Modelos Biológicos , Mutación/genética , Proteína Recombinante y Reparadora de ADN Rad52 , Recombinación Genética/genética , Proteínas de Saccharomyces cerevisiae , Telómero/genética , Transactivadores/genéticaRESUMEN
Five new metabolites have been isolated from a lyngbyastatin 1- and dolastatin 12-producing assemblage of Lyngbya majuscula and Schizothrix calcicola collected at Tumon Bay, Guam. Structure elucidation employed 2D NMR techniques and chemical derivatization. These compounds have been assigned the trivial names tumonoic acids A (2), B (1), and C (5); methyl tumonoate A (3), and methyl tumonoate B (4). Compounds 1 and 4 were also found in a lyngbyastatin 1-producing strain of L. majuscula from Guam.
Asunto(s)
Cianobacterias/química , Oligopéptidos/aislamiento & purificación , Guam , Hidrólisis , Indicadores y Reactivos , Espectroscopía de Resonancia Magnética , Oligopéptidos/química , Espectrofotometría InfrarrojaRESUMEN
Lyngbyastatin 1 (1a), a new cytotoxic analogue of dolastatins 12 (2a) and 11 (4), was isolated as an inseparable mixture with its C-15 epimer (1b) from extracts of a Lyngbya majuscula/Schizothrix calcicola assemblage and a L. majuscula strain collected near Guam. Dolastatin 12 (2a) was also encountered as an inseparable mixture with its C-15 epimer (2b) in L. majuscula/S. calcicola assemblages. At least one of the compounds in each mixture appeared to exist in solution as a mixture of slowly interconverting conformers resulting in broadened signals in 1H NMR spectra. Structure elucidation therefore relied principally on mass spectroscopy and chemical degradation studies. Both 1ab and 2ab proved toxic with only marginal or no antitumor activity when tested against colon adenocarcinoma #38 or mammary adenocarcinoma #16/C. Both 1ab and 2ab were shown to be potent disrupters of cellular microfilament networks.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Cianobacterias/química , Depsipéptidos , Oligopéptidos/aislamiento & purificación , Citoesqueleto de Actina/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular , Ensayos de Selección de Medicamentos Antitumorales , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Oligopéptidos/química , Oligopéptidos/farmacologíaRESUMEN
The past year has confirmed the great potential of the yeast Saccharomyces cerevisiae as a model to study aging. Ground breaking papers have revealed similarities between aging in yeast and in mammals, and have identified genetic instability of the ribosomal DNA array as the first known cause of aging in yeast cells.
Asunto(s)
Senescencia Celular , Saccharomyces cerevisiae/fisiología , Envejecimiento/fisiología , Animales , Senescencia Celular/genética , ADN Circular/genética , ADN Circular/fisiología , ADN de Hongos/genética , ADN de Hongos/fisiología , ADN Ribosómico/genética , ADN Ribosómico/fisiología , Humanos , Saccharomyces cerevisiae/genéticaRESUMEN
When subjected to selective conditions that impose starvation, a bacterial population can accumulate mutations, called adaptive, that allow colony formation. Here, the reversion of a lac allele under selective conditions, in a model system using Escherichia coli with the lac mutation on an F' plasmid, was shown to require the conjugational capacity of the plasmid. Reversion associated with transfer was shown, and when the same lac allele was chromosomal, reversion to Lac+ was 25 to 50 times less frequent. Postplating reversion was 25 times less when mating was inhibited by the presence of detergent. Mutability associated with conjugation provides new ways of thinking about the origin of adaptive mutations.