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1.
Nat Commun ; 12(1): 2398, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893278

RESUMO

Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show in prostate cancer cells that arginine acts as an epigenetic regulator to modulate histone acetylation, leading to global upregulation of nuclear-encoded oxidative phosphorylation (OXPHOS) genes. TEAD4 is retained in the nucleus by arginine, enhancing its recruitment to the promoter/enhancer regions of OXPHOS genes and mediating coordinated upregulation in a YAP1-independent but mTOR-dependent manner. Arginine also activates the expression of lysine acetyl-transferases and increases overall levels of acetylated histones and acetyl-CoA, facilitating TEAD4 recruitment. Silencing of TEAD4 suppresses OXPHOS functions and prostate cancer cell growth in vitro and in vivo. Given the strong correlation of TEAD4 expression and prostate carcinogenesis, targeting TEAD4 may be beneficially used to enhance arginine-deprivation therapy and prostate cancer therapy.


Assuntos
Arginina/farmacologia , Proteínas de Ligação a DNA/genética , Epigênese Genética/efeitos dos fármacos , Epigenômica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Musculares/genética , Fosforilação Oxidativa/efeitos dos fármacos , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Animais , Arginina/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Musculares/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição/metabolismo
2.
Sci Rep ; 10(1): 6428, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286458

RESUMO

It is essential for the survival and reproduction of parasitoids to adapt to the fluctuating host resources. Phenotypic plasticity may enable a parasitoid species to successfully achieve its control over a range of host species to maximize fitness in different hosts that may each require dissimilar, possibly conflicting, specific adaptations. However, there is limited information on how the fitness effects of host switching partition into costs due to the novelty of host species, where unfamiliarity with host physiological and morphological changes and its anti-parasite defenses reduces parasitoid growth, survivorship and/or reproductive success. In this study, the parasitoid fungus Ophiocordyceps unilateralis sensu lato was found to sympatrically infect a principal host ant species and other alternative sympatric hosts in the forest of central Taiwan. We herein report that the occurrence of ant infections by O. unilateralis s.l. shows spatial and temporal variation patterns on different host species. Results showed that the height from the ground to the leaf where the infected ants grip on, perithecia-forming ability, and growth rate of the stroma of the parasitoid fungus were dissimilar on different host species. These host range expansions not only related the fitness of O. unilateralis s.l. but also influenced the expression of extended phenotypic traits. Our findings revealed that a generalist parasitoid fungus suffered an evolutionary tradeoff between host breadth expansion and host-use efficiency.


Assuntos
Formigas/microbiologia , Interações Hospedeiro-Patógeno , Hypocreales/fisiologia , Simpatria/fisiologia , Animais , Ecossistema , Micoses/microbiologia , Reprodução/fisiologia , Fatores de Tempo
3.
Sci Rep ; 8(1): 10270, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980731

RESUMO

Phenotypic plasticity is the ability of a single genotype of an organism to exhibit variable phenotypes in response to fluctuating environments. It plays a crucial role in their evolutionary success. In natural environments, the importance of interactions between microalgae and other microorganisms is generally well appreciated, but the effects of these interactions on algal phenotypic plasticity has not been investigated. In this study, it revealed that indole-3-acetic acid (IAA), the most common naturally occurring plant hormone, can exert stimulatory at low concentrations and inhibitory effects at high concentrations on the growth of the green alga Desmodesmus. The morphological characteristics of Desmodesmus changed drastically under exposure to IAA compared with the algae in the control environment. The proportion of Desmodesmus unicells in monocultures increased with the IAA concentration, and these unicells exhibited less possibility of sedimentation than large cells. Furthermore, we discovered that lipid droplets accumulated in algal cells grown at a high IAA concentration. Results also demonstrated that the presence of algal competitor further stimulated inducible morphological changes in Desmodesmus populations. The relative abundance of competitors influenced the proportion of induced morphological changes. The results indicate that phenotypic plasticity in microalgae can be a response to fluctuating environments, in which algae optimize the cost-benefit ratio.


Assuntos
Adaptação Fisiológica , Ácidos Indolacéticos/farmacologia , Lipídeos/análise , Microalgas/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/farmacologia , Evolução Biológica , Clorofila/metabolismo , Meio Ambiente , Microalgas/efeitos dos fármacos , Microalgas/metabolismo
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