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肝 SH3 结构域结合激酶 1(SBK1)在小鼠和金鱼中的差异表达调控。

Differential regulation of hepatic SH3 domain binding kinase 1 (SBK1) expression in mouse and goldfish.

机构信息

School of Biological Sciences, The University of Hong Kong, Hong Kong Special Administrative Region.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.

出版信息

Gen Comp Endocrinol. 2023 Dec 1;344:114372. doi: 10.1016/j.ygcen.2023.114372. Epub 2023 Aug 29.

Abstract

SH3 domain binding kinase 1 (SBK1) is a serine/threonine kinase that belongs to the new kinase family (NFK) with limited information on its function. Previous studies reported that SBK1 plays a role in memory formation, lipid metabolism, and cancer cell progression. Nevertheless, the regulatory mechanism of Sbk1 expression in various tissues remains unknown. We report here that Sbk1 expression in mouse hepatocytes was downregulated by glucocorticoid, whereas saturated and unsaturated fatty acids were stimulators of Sbk1 expression. The regulatory role of glucocorticoid and fatty acid was further confirmed by the Sbk1 promoter assay, which aligned with the presence of several glucocorticoid-response elements (GRE) and peroxisome proliferator responsive elements (PPRE) in the mouse Sbk1 promoter. The inhibitory effect of glucocorticoids on hepatic Sbk1 expression and protein content could also be demonstrated in vivo after prednisolone injection. Moreover, the expression of SBK1 in goldfish (gfSBK1) was also sensitive to glucocorticoid suppression as their mouse orthologues. In contrast, insulin had a differential action on SBK1 expression that it promoted the expression of all SBK1 isoforms in the goldfish hepatocytes but inhibited Sbk1 expression in the mouse hepatocytes. Together, our findings indicate that SBK1 expression is hormone- and nutrient-sensitive with a species-specific response.

摘要

SH3 结构域结合激酶 1(SBK1)是一种丝氨酸/苏氨酸激酶,属于新激酶家族(NFK),其功能信息有限。先前的研究表明,SBK1 在记忆形成、脂质代谢和癌细胞进展中发挥作用。然而,各种组织中 Sbk1 表达的调控机制尚不清楚。我们在这里报告,糖皮质激素下调了小鼠肝细胞中 Sbk1 的表达,而饱和和不饱和脂肪酸则是 Sbk1 表达的刺激物。通过 Sbk1 启动子测定进一步证实了糖皮质激素和脂肪酸的调节作用,该测定与小鼠 Sbk1 启动子中存在几个糖皮质激素反应元件(GRE)和过氧化物酶体增殖物反应元件(PPRE)一致。在给予泼尼松龙注射后,也可以在体内证明糖皮质激素对肝 Sbk1 表达和蛋白含量的抑制作用。此外,金鱼(gfSBK1)的 SBK1 表达也对糖皮质激素的抑制敏感,因为它们的小鼠同源物也是如此。相比之下,胰岛素对 SBK1 表达具有不同的作用,它促进了金鱼肝细胞中所有 SBK1 同工型的表达,但抑制了小鼠肝细胞中 Sbk1 的表达。总之,我们的研究结果表明,SBK1 表达受激素和营养物质的影响,具有物种特异性反应。

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