RESUMO
Kir4.1, a glial-specific K+ channel, is critical for normal CNS development. Studies using both global and glial-specific knockout of Kir4.1 reveal abnormal CNS development with the loss of the channel. Specifically, Kir4.1 knockout animals are characterized by ataxia, severe hypomyelination, and early postnatal death. Additionally, Kir4.1 has emerged as a key player in several CNS diseases. Notably, decreased Kir4.1 protein expression occurs in several human CNS pathologies including CNS ischemic injury, spinal cord injury, epilepsy, ALS, and Alzheimer's disease. Despite the emerging significance of Kir4.1 in normal and pathological conditions, its mechanisms of regulation are unknown. Here, we report the first epigenetic regulation of a K+ channel in the CNS. Robust developmental upregulation of Kir4.1 expression in rats is coincident with reductions in DNA methylation of the Kir4.1 gene, KCNJ10. Chromatin immunoprecipitation reveals a dynamic interaction between KCNJ10 and DNA methyltransferase 1 during development. Finally, demethylation of the KCNJ10 promoter is necessary for transcription. These findings indicate DNA methylation is a key regulator of Kir4.1 transcription. Given the essential role of Kir4.1 in normal CNS development, understanding the regulation of this K+ channel is critical to understanding normal glial biology.
Assuntos
Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Metilação de DNA/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Ilhas de CpG/genética , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/metabolismo , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteína Glial Fibrilar Ácida/metabolismo , Células HEK293 , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismoRESUMO
Central giant cell granuloma formerly called as giant cell reparative granuloma is a non neoplastic proliferative lesion of unknown etiology. It occurs most commonly in mandible, but can also occur in maxilla. The case described here involved maxilla which was treated with surgical excision.
RESUMO
Small Cell Neuroendocrine Carcinomas of the Sinonasal tract are extremely uncommon and distinct neoplasms with aggressive clinical behavior. They have similar morphological and immunohistochemical features to those of small cell carcinomas of the lung. They should be distinguished from Olfactory Neuroblastomas. We report a case of this rare entity.A 46-year-old woman presented with a history of injury to the right eye with facial pain and proptosis as the primary symptoms. Later she developed nasal stuffiness. C.T. Scan revealed a space occupying lesion in the right nostril extending into ethmoid sinus and orbit. Functional endoscopic sinus surgery was done with decompression of the orbit. The biopsy material was obtained from ethmoid sinus and orbit. Histopathological examination of the biopsy specimen along with Immunohistochemical stains confirmed a Small Cell Neuroendocrine Carcinoma. Patient was treated with Radiotherapy and chemotherapy and responded well.