RESUMO
In adipose tissue, D-dopachrome tautomerase (DDT), a cytokine with structural similarity to macrophage migration inhibitory factor, is mainly expressed in adipocytes rather than preadipocytes and acts as an anti-obesity adipokine in an autocrine manner. However, its transcriptional regulation is largely unknown. In order to explore molecules affecting DDT transcription, a chemical library screening using HEK293 cells stably expressing a DDT promoter-reporter construct was performed. Several derivatives of 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, were identified as transcriptional activators of the DDT gene. Furthermore, DDT mRNA levels were reduced in SGBS adipocytes treated with compound C, an AMPK inhibitor, suggesting involvement of AMPK in DDT transcription. Overexpression of the FOXO1 constitutive active form reduced transcriptional activity of the DDT gene in SGBS cells, but increased it in HEK293 cells. Cell-type specific effects were also observed in the DDT gene expression of cells treated with AS1842856, a FOXO1 inhibitor. Finally, involvement of the mammalian target of rapamycin (mTOR) signaling in DDT transcription in SGBS adipocytes was investigated. Rapamycin, an inhibitor of mTOR, increased DDT mRNA levels and attenuated the inhibitory effects of compound C on DDT mRNA levels in SGBS adipocytes. In conclusion, DDT transcription may be regulated in a cell-dependent manner, and were enhanced by AMPK activation in SGBS adipocytes through inhibiting the mTOR signaling.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/fisiologia , Diferenciação Celular , Oxirredutases Intramoleculares/genética , Serina-Treonina Quinases TOR/metabolismo , Transcrição Gênica , Adipócitos/efeitos dos fármacos , Linhagem Celular , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica , Células HEK293 , Humanos , Transdução de Sinais , Sirolimo/farmacologiaRESUMO
We present herein the imaging and pathological features of a 28-year-old male with a sinonasal hemangiopericytoma-like tumor occupying the left nasal meatus. At the initial visit, a nasal polyp was suspected, but, as the patient was bleeding readily, an angiomatoid lesion was also regarded as a possible diagnosis. Based on a thorough histopathological analysis, a sinonasal hemangiopericytoma-like tumor was diagnosed. Hematoxylin and eosin staining also showed a mild degree of nuclear pleomorphism and a slight increase in mitotic activity, and immunohistochemical studies using anti-CD34, MIB-1, and Vimentin antibodies were useful for distinguishing the hemangiopericytoma-like tumor from true hemangiopericytoma and a solitary fibrous tumor.