RESUMO
Spermatogenesis is a very complex process with an intricate transcriptional regulation. The transition from the diploid to the haploid state requires the involvement of specialized genes in meiosis, among other specific functions for the formation of the spermatozoon. The transcription factor cAMP-response element modulator (CREM) is a key modulator that triggers the differentiation of the germ cell into the spermatozoon through the modification of gene expression. CREM has multiple repressor and activator isoforms whose expression is tissue-cell-type specific and tightly regulated by various factors at the transcriptional, post-transcriptional and post-translational level. The activator isoform CREMτ controls the expression of several relevant genes in post-meiotic stages of spermatogenesis. In addition, exposure to xenobiotics negatively affects CREMτ expression, which is linked to male infertility. On the other hand, antioxidants could have a positive effect on CREMτ expression and improve sperm parameters in idiopathically infertile men. Therefore, CREM expression could be used as a biomarker to detect and even counteract male infertility. This review examines the importance of CREM as a transcription factor for sperm production and its relevance in male fertility, infertility and the response to environmental xenobiotics that may affect CREMτ expression and the downstream regulation that alters male fertility. Also, some health disorders in which CREM expression is altered are discussed.
Assuntos
Infertilidade Masculina , Xenobióticos , Masculino , Humanos , Sêmen , Espermatogênese/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Infertilidade Masculina/genética , Meiose , Elementos de Resposta , Fertilidade/genética , Modulador de Elemento de Resposta do AMP Cíclico/genéticaRESUMO
CATSPER2 (Cation channel sperm-associated protein 2) protein, which is part of the calcium CATSPER channel located in the membrane of the flagellar principal piece of the sperm cell, is only expressed in the testis during spermatogenesis. Deletions or mutations in the Catsper2 gene are associated with the deafness-infertility syndrome (DIS) and non-syndromic male infertility. However, the mechanisms by which Catsper2 is regulated are unknown. Here, we report the characterization of the promoter region of murine Catsper2 and the role of CTCF and CREMτ in its transcription. We report that the promoter region has transcriptional activity in both directions, as determined by observing luciferase activity in mouse Sertoli and GC-1 spg transfected cells. WGBS data analysis indicated that a CpG island identified in silico is non-methylated; Chromatin immunoprecipitation (ChIP)-seq data analysis revealed that histone marks H3K4me3 and H3K36me3 are present in the promoter and body of the Catsper2 gene respectively, indicating that Catsper2 is subject to epigenetic regulation. In addition, the murine Catsper2 core promoter was delimited to a region between -54/+189 relative to the transcription start site (TSS), where three CTCF and one CRE binding site were predicted. The functionality of these sites was determined by mutation of the CTCF sites and deletion of the CRE site. Finally, ChIP assays confirmed that CREMτ and CTCF bind to the Catsper2 minimal promoter region. This study represents the first functional analysis of the murine Catsper2 promoter region and the mechanisms that regulate its expression.
Assuntos
Canais de Cálcio , Epigênese Genética , Regiões Promotoras Genéticas , Proteínas de Plasma Seminal , Animais , Masculino , Camundongos , Sítios de Ligação , Canais de Cálcio/genética , Regulação da Expressão Gênica , Proteínas de Plasma Seminal/genéticaRESUMO
The group of CNS mesenchymal (non-meningothelial) and primary glial/neuronal tumors in association with EWSR1-non-ETS rearrangements comprises a growing spectrum of entities, mostly reported in isolation with incomplete molecular profiling. Archival files from three pediatric institutions were queried for unusual cases of pediatric (≤21 years) CNS EWSR1-rearranged tumors confirmed by at least one molecular technique. Extra-axial tumors and cases with a diagnosis of Ewing sarcoma (EWSR1-ETS family fusions) were excluded. Additional studies, including anchored multiplex-PCR with next-generation sequencing and DNA methylation profiling, were performed as needed to determine fusion partner status and brain tumor methylation class, respectively. Five cases (median 17 years) were identified (M:F of 3:2). Location was parenchymal (n = 3) and undetermined (n = 2) with topographic distributions including posterior fossa (n = 1), frontal (n = 1), temporal (n = 1), parietal (n = 1) and occipital (n = 1) lobes. Final designation with fusion findings included desmoplastic small round cell tumor (EWSR1-WT1; n = 1) and tumors of uncertain histogenesis (EWSR1-CREM, n = 1; EWSR1-CREB1, n = 1; EWSR1-PLAGL1, n = 1; and EWSR1-PATZ1, n = 1). Tumors showed a wide spectrum of morphology and biologic behavior. For EWSR1-CREM, EWSR1-PLAGL1 and EWSR1-PATZ1 tumors, no significant methylation scores were reached in the known brain tumor classes. Available outcome (4/5) was reported as favorable (n = 2) and unfavorable (n = 2) with a median follow-up of 30 months. In conclusion, we describe five primary EWSR1-non-ETS fused CNS tumors exhibiting morphologic and biologic heterogeneity and we highlight the clinical importance of determining specific fusion partners to improve diagnostic accuracy, treatment and monitoring. Larger prospective clinicopathological and molecular studies are needed to determine the prognostic implications of histotypes, anatomical location, fusion partners, breakpoints and methylation profiles in patients with these rare tumors.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Proteína EWS de Ligação a RNA/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fusão Oncogênica , Proteínas de Fusão Oncogênica/genética , Adulto JovemRESUMO
The molecular and intracellular signaling processes that control sleep and wake states remain largely unknown. A consistent observation is that the cyclic adenosine monophosphate (AMP) response element-binding protein (CREB), an activity-dependent transcription factor, is differentially activated during sleep and wakefulness. CREB is phosphorylated by the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway as well as other kinases, and phosphorylated CREB promotes the transcription of target genes. Genetic studies in flies and mice suggest that CREB signaling influences sleep/wake states by promoting and stabilizing wakefulness. However, it remains unclear where in the brain CREB is required to drive wakefulness. In rats, CREB phosphorylation increases in the cerebral cortex during wakefulness and decreases during sleep, but it is not known if this change is functionally relevant to the maintenance of wakefulness. Here, we used the Cre/lox system to conditionally delete CREB in the forebrain (FB) and in the locus coeruleus (LC), two regions known to be important for the production of arousal and wakefulness. We used polysomnography to measure sleep/wake levels and sleep architecture in conditional CREB mutant mice and control littermates. We found that FB-specific deletion of CREB decreased wakefulness and increased non-rapid eye movement sleep. Mice lacking CREB in the FB were unable to sustain normal periods of wakefulness. On the other hand, deletion of CREB from LC neurons did not change sleep/wake levels or sleep/wake architecture. Taken together, these results suggest that CREB is required in neurons within the FB but not in the LC to promote and stabilize wakefulness.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Vigília , Animais , Córtex Cerebral/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Camundongos , Neurônios/metabolismo , Ratos , SonoRESUMO
A Tropaeolum pentaphyllum Lam é uma Planta Alimentícia Não Convencional (PANC) nativa do Brasil, que está em crescente estudo. O objetivo deste trabalho foi avaliar a composição físico-química, o pH e cor da polpa da batata. Observou-se que a umidade (79,32 %), proteína (2,33%) e cinzas (0,93%), apresentaram-se semelhantes à T. pentaphyllum Lam avaliadas em outros estudos. Já os teores de carboidratos (13,02%), valor energético (82,19%) e lipídeos (3,82%) apresentaram-se superiores e de fibras (1,78%) inferiores a vegetais da mesma espécie. Além disso, a planta mostrou-se ácida, luminosa e com coloração tendendo ao vermelho e ao amarelo. Assim, percebe-se que a batata pode ser considerada um complemento alimentar pela sua composição nutricional e que é necessário a realização de mais estudos, a fim de aprimorar o conhecimento sobre a mesma.
Assuntos
Composição de Alimentos , Cor , Fenômenos Químicos , Tropaeolum/química , Concentração de Íons de HidrogênioRESUMO
A Tropaeolum pentaphyllum Lam é uma Planta Alimentícia Não Convencional (PANC) nativa do Brasil, que está em crescente estudo. O objetivo deste trabalho foi avaliar a composição físico-química, o pH e cor da polpa da batata. Observou-se que a umidade (79,32 %), proteína (2,33%) e cinzas (0,93%), apresentaram-se semelhantes à T. pentaphyllum Lam avaliadas em outros estudos. Já os teores de carboidratos (13,02%), valor energético (82,19%) e lipídeos (3,82%) apresentaram-se superiores e de fibras (1,78%) inferiores a vegetais da mesma espécie. Além disso, a planta mostrou-se ácida, luminosa e com coloração tendendo ao vermelho e ao amarelo. Assim, percebe-se que a batata pode ser considerada um complemento alimentar pela sua composição nutricional e que é necessário a realização de mais estudos, a fim de aprimorar o conhecimento sobre a mesma.(AU)
Assuntos
Tropaeolum/química , Fenômenos Químicos , Composição de Alimentos , Cor , Concentração de Íons de HidrogênioRESUMO
A Tropaeolum pentaphyllum Lam é uma Planta Alimentícia Não Convencional (PANC) nativa do Brasil em crescente estudo. O presente trabalho objetivou avaliar a composição química, cor da polpa e pH da planta submetida à fritura e à conserva salgada acidificada. As amostras foram submetidas à higienização, corte em lâminas, seguido dos processos de cocção, trituração e posterior análise físico-química. Observou-se na amostra frita valores mais elevados para proteínas (4,12%), lipídeos (11,66%), potássio (364,78mg/100g), pH 4,84 e tendência à coloração amarela. Quando comparada a amostras em conserva, que apresentaram maior valor de umidade (76,88%) e de sódio (544,17mg/100g), com tendência à coloração vermelha. Assim, conclui-se que houve influência dos métodos de cocção nas características das amostras.
Assuntos
Tropaeolum/química , Fenômenos Químicos , Alimentos em ConservaRESUMO
Learning and memory are basic functions of the brain that allowed human evolution. It is well accepted that during learning and memory formation the dynamic establishment of new active synaptic connections is crucial. Persistent synaptic activation leads to molecular events that include increased release of neurotransmitters, increased expression of receptors on the postsynaptic neuron, thus creating a positive feedback that results in the activation of distinct signaling pathways that temporally and permanently alter specific patterns of gene expression. However, the epigenetic changes that allow the establishment of long term genetic programs that control learning and memory are not completely understood. Even less is known regarding the signaling events triggered by synaptic activity that regulate these epigenetic marks. Here we review the current understanding of the molecular mechanisms controlling activity-dependent gene transcription leading synaptic plasticity and memory formation. We describe how Ca(2+) entry through N-methyl-d-aspartate-type glutamate neurotransmitter receptors result in the activation of specific signaling pathways leading to changes in gene expression, giving special emphasis to the recent data pointing out different epigenetic mechanisms (histone acetylation, methylation and phosphorylation as well as DNA methylation and hydroxymethylation) underlying learning and memory.