RESUMO
Esophageal cancer is a prominent worldwide illness that is divided into two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Mortality rates are alarming, and the understanding of the mechanisms involved in esophageal cancer development, becomes essential. Purinergic signaling is related to many diseases and among these various types of tumors. Here we studied the effects of the P2Y2 receptor activation in different types of esophageal cancer. Esophageal tissue samples of healthy controls were used for P2Y2R expression quantification. Two human esophageal cancer cell lines Kyse-450 (squamous cell carcinoma) and OE-33 (adenocarcinoma) were used to perform in vitro analysis of cell proliferation, migration, adhesion, and the signaling pathways involved in P2Y2R activation. Data showed that P2Y2R was expressed in biopsies of patients with ESCC and adenocarcinoma, as well as in the two human esophageal cancer cell lines studied. The RT-qPCR analysis demonstrated that OE-33 cells have higher P2RY2 expression than Kyse-450 squamous cell line. Results showed that P2Y2R activation, induced by ATP or UTP, promoted esophageal cancer cells proliferation and colony formation. P2Y2R blockage with the selective antagonist, AR-C 118925XX, led to decreased proliferation, colony formation and adhesion. Treatments with ATP or UTP activated ERK 1/2 pathway in ESCC and ECA cells. The P2Y2R antagonism did not alter the migration of esophageal cancer cells. Interestingly, the esophageal cancer cell lines presented a distinct profile of nucleotide hydrolysis activity. The modulation of P2Y2 receptors may be a promising target for esophageal cancer treatment.
Assuntos
Adenocarcinoma/enzimologia , Carcinoma de Células Escamosas/enzimologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Agonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y2/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Trifosfato de Adenosina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y2/metabolismo , Transdução de Sinais , Uridina Trifosfato/farmacologiaAssuntos
Depressão/metabolismo , Receptor A2A de Adenosina/metabolismo , Suicídio/psicologia , Adenosina/metabolismo , Depressão/fisiopatologia , Transtorno Depressivo/metabolismo , Transtorno Depressivo/fisiopatologia , Humanos , Comportamento Impulsivo/fisiologia , Receptor A2A de Adenosina/efeitos dos fármacos , Receptores Purinérgicos/metabolismo , Ideação SuicidaRESUMO
Neurogenesis is the process by which new neurons are generated in the brain. Neural stem cells (NSCs) are differentiated into neurons, which are integrated into the neural network. Nowadays, pluripotent stem cells, multipotent stem cells, and induced pluripotent stem cells can be artificially differentiated into neurons utilizing several techniques. Specific transcriptional profiles from NSCs during differentiation are frequently used to approach and observe phenotype alteration and functional determination of neurons. In this context, the role of non-coding RNA, transcription factors and epigenetic changes in neuronal development and differentiation has gained importance. Epigenetic elucidation has become a field of intense research due to distinct patterns of normal conditions and different neurodegenerative disorders, which can be explored to develop new diagnostic methods or gene therapies. In this review, we discuss the complexity of transcription factors, non-coding RNAs, and extracellular vesicles that are responsible for guiding and coordinating neural development.
Assuntos
Diferenciação Celular/genética , Epigênese Genética , Neurônios/citologia , Neurônios/metabolismo , Transdução de Sinais/genética , Animais , Exossomos/metabolismo , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismoRESUMO
Since proving adenosine triphosphate (ATP) functions as a neurotransmitter in neuron/glia interactions, the purinergic system has been more intensely studied within the scope of the central nervous system. In neurological disorders with associated motor symptoms, including Parkinson's disease (PD), motor neuron diseases (MND), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's Disease (HD), restless leg syndrome (RLS), and ataxias, alterations in purinergic receptor expression and activity have been noted, indicating a potential role for this system in disease etiology and progression. In neurodegenerative conditions, neural cell death provokes extensive ATP release and alters calcium signaling through purinergic receptor modulation. Consequently, neuroinflammatory responses, excitotoxicity and apoptosis are directly or indirectly induced. This review analyzes currently available data, which suggests involvement of the purinergic system in neuro-associated motor dysfunctions and underlying mechanisms. Possible targets for pharmacological interventions are also discussed.
RESUMO
Neuropsychiatric disorders involve various pathological mechanisms, resulting in neurodegeneration and brain atrophy. Neurodevelopmental processes have shown to be critical for the progression of those disorders, which are based on genetic and epigenetic mechanisms as well as on extrinsic factors. We review here common mechanisms underlying the comorbidity of Bipolar Disorders and Alzheimer's Disease, such as aberrant neurogenesis and neurotoxicity, reporting current therapeutic approaches. The understanding of these mechanisms precedes stem cell-based strategies as a new therapeutic possibility for treatment and prevention of Bipolar and Alzheimer's Disease progression. Taking into account the difficulty of studying the molecular basis of disease progression directly in patients, we also discuss the importance of stem cells for effective drug screening, modeling and treating psychiatric diseases, once in vitro differentiation of patient-induced pluripotent stem cells provides relevant information about embryonic origins, intracellular pathways and molecular mechanisms.