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1.
Sci Rep ; 10(1): 21533, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33299042

RESUMO

The interneurons of the olfactory bulb (OB) are characterized by the expression of different calcium-binding proteins, whose specific functions are not fully understood. This is the case of one of the most recently discovered, the secretagogin (SCGN), which is expressed in interneurons of the glomerular and the granule cell layers, but whose function in the olfactory pathway is still unknown. To address this question, we examined the distribution, generation and activity of SCGN-positive interneurons in the OB of two complementary models of olfactory impairments: Purkinje Cell Degeneration (PCD) and olfactory-deprived mice. Our results showed a significant increase in the density of SCGN-positive cells in the inframitral layers of olfactory-deprived mice as compared to control animals. Moreover, BrdU analyses revealed that these additional SCGN-positive cells are not newly formed. Finally, the neuronal activity, estimated by c-Fos expression, increased in preexisting SCGN-positive interneurons of both deprived and PCD mice -being higher in the later- in comparison with control animals. Altogether, our results suggest that the OB possesses different compensatory mechanisms depending on the type of alteration. Particularly, the SCGN expression is dependent of olfactory stimuli and its function may be related to a compensation against a reduction in sensory inputs.


Assuntos
Interneurônios/metabolismo , Bulbo Olfatório/patologia , Secretagoginas/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Odorantes , Bulbo Olfatório/metabolismo , Condutos Olfatórios/fisiologia , Percepção Olfatória/fisiologia , Secretagoginas/fisiologia , Olfato/fisiologia
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 45(1): 56-60, 2016 01.
Artigo em Chinês | MEDLINE | ID: mdl-27045242

RESUMO

Secretagogin (SCGN) is a novel member of EF-hand Ca2+-binding proteins, which was identified in islet ß cells by Wagner. SCGN is a six EF-hand Ca2+-binding protein, primarily expressed on the neuroendocrine axis and the central nervous system. The protein has abundant biological functions. A certain concentration of calcium ion can lead to conformation change of SCGN, resulting in the change of intracellular signal transduction. Preliminary studies showed that SCGN would be used to treat stress reaction, such as mental illness (depression), burns or post-traumatic stress disorder and chronic stress reaction caused by pain. In Alzheimer's disease, the expression of SCGN in the hippocampus can boycott neurodegeneration. In neuroendocrine tumors, SCGN presents a good consistency with neuroendocrine markers such as CgA, Syn, and NSE, with a higher overall sensitivity and specificity. In addition, SCGN is released into serum after neural damage in cerebral ischemic diseases, suggesting that SCGN can be used as a marker for brain trauma. In this article, we review the recent research progress of secretagogin, focus on its distribution and functions in various tumorous diseases and non-tumorous diseases, such as Alzheimer's disease.


Assuntos
Secretagoginas/fisiologia , Doença de Alzheimer/diagnóstico , Biomarcadores/análise , Isquemia Encefálica/diagnóstico , Cálcio/metabolismo , Hipocampo/metabolismo , Humanos , Tumores Neuroendócrinos/diagnóstico , Transdução de Sinais
3.
PLoS One ; 11(3): e0151927, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26986842

RESUMO

Elucidating the regulation of glucose-stimulated insulin secretion (GSIS) in pancreatic ß cells is important for understanding and treating diabetes. The pancreatic ß cell line, MIN6, retains GSIS but gradually loses it in long-term culture. The MIN6 subclone, MIN6c4, exhibits well-regulated GSIS even after prolonged culture. We previously used DNA microarray analysis to compare gene expression in the parental MIN6 cells and MIN6c4 cells and identified several differentially regulated genes that may be involved in maintaining GSIS. Here we investigated the potential roles of six of these genes in GSIS: Tmem59l (Transmembrane protein 59 like), Scgn (Secretagogin), Gucy2c (Guanylate cyclase 2c), Slc29a4 (Solute carrier family 29, member 4), Cdhr1 (Cadherin-related family member 1), and Celsr2 (Cadherin EGF LAG seven-pass G-type receptor 2). These genes were knocked down in MIN6c4 cells using lentivirus vectors expressing gene-specific short hairpin RNAs (shRNAs), and the effects of the knockdown on insulin expression and secretion were analyzed. Suppression of Tmem59l, Scgn, and Gucy2c expression resulted in significantly decreased glucose- and/or KCl-stimulated insulin secretion from MIN6c4 cells, while the suppression of Slc29a4 expression resulted in increased insulin secretion. Tmem59l overexpression rescued the phenotype of the Tmem59l knockdown MIN6c4 cells, and immunostaining analysis indicated that the TMEM59L protein colocalized with insulin and GM130, a Golgi complex marker, in MIN6 cells. Collectively, our findings suggested that the proteins encoded by Tmem59l, Scgn, Gucy2c, and Slc29a4 play important roles in regulating GSIS. Detailed studies of these proteins and their functions are expected to provide new insights into the molecular mechanisms involved in insulin secretion.


Assuntos
Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Animais , Western Blotting , Caderinas/fisiologia , Linhagem Celular , Feminino , Imunofluorescência , Técnicas de Silenciamento de Genes , Genes Reguladores/fisiologia , Glucose/fisiologia , Insulina/fisiologia , Secreção de Insulina , Células Secretoras de Insulina/fisiologia , Proteínas de Membrana/fisiologia , Proteínas de Membrana Transportadoras/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase/fisiologia , Receptores de Peptídeos/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Secretagoginas/fisiologia
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