RESUMEN
Apoptosis is an essential physiological process that controls many important biological functions. However, apoptosis signaling in relation to secondary metabolite biosynthesis in plants and fungi remains a mystery. The fungus Ganoderma lucidum is a popular herbal medicine worldwide, but the biosynthetic regulation of its active ingredients (ganoderic acids, GAs) is poorly understood. We investigated the role of 3',5'-cyclic adenosine monophosphate (cAMP) signaling in fungal apoptosis and GA biosynthesis in G. lucidum. Two phosphodiesterase inhibitors (caffeine and 3-isobutyl-1-methylxanthine, IBMX) and an adenylate cyclase activator (sodium fluoride, NaF) were used to increase intracellular cAMP levels. Fungal apoptosis was identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and a condensed nuclear morphology. Our results showed that GA production and fungal apoptosis were induced when the mycelium was treated with NaF, caffeine, or cAMP/IBMX. Downregulation of squalene synthase and lanosterol synthase gene expression by cAMP was detected in the presence of these chemicals, which indicates that these two genes are not critical for GA induction. Transcriptome analysis indicated that mitochondria might play an important role in cAMP-induced apoptosis and GA biosynthesis. To the best of our knowledge, this is the first report to reveal that cAMP signaling induces apoptosis and secondary metabolite production in fungi.
Asunto(s)
AMP Cíclico/metabolismo , Inhibidores de Fosfodiesterasa/farmacología , Reishi/efectos de los fármacos , Fluoruro de Sodio/farmacología , Triterpenos/metabolismo , 1-Metil-3-Isobutilxantina/farmacología , Apoptosis , Vías Biosintéticas/efectos de los fármacos , Cafeína/farmacología , Farnesil Difosfato Farnesil Transferasa/genética , Farnesil Difosfato Farnesil Transferasa/metabolismo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Transferasas Intramoleculares/genética , Transferasas Intramoleculares/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Reishi/citología , Reishi/genética , Reishi/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Aging is highly correlated with the progressive loss of physiological function, including cognitive behavior and reproductive capacity, as well as an increased susceptibility to diseases; therefore, slowing age-related degeneration could greatly contribute to human health. Cynomorium songaricum Rupr. (CS) is traditionally used to improve sexual function and treat kidney dysfunction in traditional Chinese medicine, although little is known about whether CS has effects on longevity. Here, we show that CS supplementation in the diet extends both the mean and maximum lifespan of adult female flies. The increase in lifespan with CS was correlated with higher resistance to oxidative stress and starvation and lower lipid hydroperoxides (LPO) levels. Additionally, the lifespan extension was accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppression of age-related learning impairment in aged flies. These findings demonstrate the important antiaging effects of CS and indicate the potential applicability of dietary intervention with CS to enhance health and prevent multiple age-related diseases.