Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cells ; 13(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38534317

RESUMO

Mitochondria provide energy for all cellular processes, including reactions associated with cell cycle progression, DNA damage repair, and cilia formation. Moreover, mitochondria participate in cell fate decisions between death and survival. Nek family members have already been implicated in DNA damage response, cilia formation, cell death, and cell cycle control. Here, we discuss the role of several Nek family members, namely Nek1, Nek4, Nek5, Nek6, and Nek10, which are not exclusively dedicated to cell cycle-related functions, in controlling mitochondrial functions. Specifically, we review the function of these Neks in mitochondrial respiration and dynamics, mtDNA maintenance, stress response, and cell death. Finally, we discuss the interplay of other cell cycle kinases in mitochondrial function and vice versa. Nek1, Nek5, and Nek6 are connected to the stress response, including ROS control, mtDNA repair, autophagy, and apoptosis. Nek4, in turn, seems to be related to mitochondrial dynamics, while Nek10 is involved with mitochondrial metabolism. Here, we propose that the participation of Neks in mitochondrial roles is a new functional axis for the Nek family.


Assuntos
Mitocôndrias , Proteínas Serina-Treonina Quinases , Quinases Relacionadas a NIMA/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Mitocôndrias/metabolismo , Homeostase , DNA Mitocondrial
2.
J Vis Exp ; (170)2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33970143

RESUMO

mRNA processing involves multiple simultaneous steps to prepare mRNA for translation, such as 5´capping, poly-A addition and splicing. Besides constitutive splicing, alternative mRNA splicing allows the expression of multifunctional proteins from one gene. As interactome studies are generally the first analysis for new or unknown proteins, the association of the bait protein with splicing factors is an indication that it can participate in mRNA splicing process, but to determine in what context or what genes are regulated is an empirical process. A good starting point to evaluate this function is using the classical minigene tool. Here we present the adenoviral E1A minigene usage for evaluating the alternative splicing changes after different cellular stress stimuli. We evaluated the splicing of E1A minigene in HEK293 stably overexpressing Nek4 protein after different stressing treatments. The protocol includes E1A minigene transfection, cell treatment, RNA extraction and cDNA synthesis, followed by PCR and gel analysis and quantification of the E1A spliced variants. The use of this simple and well-established method combined with specific treatments is a reliable starting point to shed light on cellular processes or what genes can be regulated by mRNA splicing.


Assuntos
Processamento Alternativo , RNA Mensageiro/genética , DNA Complementar/genética , Células HEK293 , Humanos , Mutação , Transfecção
3.
Peptides ; 37(2): 216-24, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22868213

RESUMO

Endothelial dysfunction has been implicated in portal vein obstruction, a condition responsible for major complications in chronic portal hypertension. Increased vascular tone due to disruption of endothelial function has been associated with an imbalance in the equilibrium between endothelium-derived relaxing and contracting factors. Herein, we assessed underlying mechanisms by which expression of bradykinin B(1) receptor (B(1)R) is induced in the endothelium and how its stimulation triggers vasoconstriction in the rat portal vein. Prolonged in vitro incubation of portal vein resulted in time- and endothelium-dependent expression of B(1)R and cyclooxygenase-2 (COX-2). Inhibition of protein kinase C (PKC) or phosphatidylinositol 3-kinase (PI3K) significantly reduced expression of B(1)R through the regulation of transcription factors, activator protein-1 (AP-1) and cAMP response element-binding protein (CREB). Moreover, pharmacological studies showed that B(1)R-mediated portal vein contraction was reduced by COX-2, but not COX-1, inhibitors. Notably, activation of endothelial B(1)R increased phospholipase A(2)/COX-2-derived thromboxane A(2) (TXA(2)) levels, which in turn mediated portal vein contraction through binding to TXA(2) receptors expressed in vascular smooth muscle cells. These results provide novel molecular mechanisms involved in the regulation of B(1)R expression and identify a critical role for the endothelial B(1)R in the modulation of portal vein vascular tone. Our study suggests a potential role for B(1)R antagonists as therapeutic tools for diseases where portal hypertension may be involved.


Assuntos
Bradicinina/farmacologia , Endotélio/metabolismo , Veia Porta/efeitos dos fármacos , Receptor B1 da Bradicinina/metabolismo , Vasoconstrição/efeitos dos fármacos , Animais , Bradicinina/análogos & derivados , Relação Dose-Resposta a Droga , Masculino , Veia Porta/metabolismo , Ratos , Ratos Wistar , Receptor B1 da Bradicinina/biossíntese , Relação Estrutura-Atividade
4.
Glycobiology ; 17(8): 795-804, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17522108

RESUMO

Extracts from the plant Synadenium carinatum latex are widely and indiscriminately used in popular medicine to treat a great number of inflammatory disorders and although the mechanisms underlying these effects remain undefined, the lectin isolated from S. carinatum latex (ScLL) is thought to be in part responsible for these anti-inflammatory effects. In order to elucidate possible immunoregulatory activities of ScLL, we investigated the effects of ScLL administration in models of acute and chronic inflammation. Oral administration of ScLL significantly inhibited neutrophil and eosinophil extravasation in models of acute and chronic inflammation and reduced eosinophil and mononuclear blood counts during chronic inflammation. ScLL administration reduced IL(interleukin)-4 and IL-5 levels but increased interferon-gamma and IL-10 in an asthma inflammatory model, which suggested that it might induce a TH2 to TH1 shift in the adaptive immune response. ScLL also inhibited IkappaBalpha degradation, a negative regulator of proinflammatory NF-kappaB. Taken together, these results provide the first description of a single factor isolated from S. carinatum latex extract with immunoregulatory functions and suggest that ScLL may be useful in the treatment of allergic inflammatory disorders.


Assuntos
Antiasmáticos/farmacologia , Galectinas/farmacologia , Magnoliopsida/química , Animais , Antiasmáticos/administração & dosagem , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Galectinas/administração & dosagem , Látex/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Células Th2/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...