Bock Hugo, Zimmer Aline Rigon, Zimmer Eduardo Rigon, de Souza Diogo Onofre Gomes, Portela Luis Valmor Cruz, Saraiva-Pereira Maria Luiza
Laboratório de Identificação Genética-Centro de Pesquisa Experimental e Serviço de Genética Médica-Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Mol Neurobiol. 2015 Aug;52(1):710-8. doi: 10.1007/s12035-014-8905-4. Epub 2014 Oct 4.
The 14-3-3 protein family takes part in a wide range of cellular processes and is expressed in all eukaryotic organisms. In mammals, seven isoforms (β, ε, η, γ, τ, ζ, and σ) have been identified. 14-3-3 proteins are suggested to modulate the insulin-signaling cascade in the brain. The aim of this study was to investigate whether insulin resistance state induced by high palatable diet modulates expression of the 14-3-3 proteins in brain. Wistar male rats (n = 8) were divided into two experimental groups: insulin resistant (IR), induced by high palatable diet, and control (CO) group. Biochemical parameters (glucose tolerance test and plasma lipid profile) were evaluated after 130 days. Brain structures (cortex and hippocampus) were dissected for evaluation of messenger RNA (mRNA) and protein levels of different 14-3-3 proteins. Statistical analyses included Student t test and Pearson correlation. Significant decrease was observed in Ywhah and in Ywahq mRNA levels in the cortex of IR group, while no changes were observed in the hippocampus. Significant increase of θ isoform was observed in hippocampus IR group by immunodetection, while no differences were detected in the remaining isoforms. Inverse correlation was observed between blood glucose levels in cortex IR group and both Ywhah and Ywhaq mRNA levels. Protein levels of Creb and phosphatidylinositide 3-kinases (PI3K) showed to be increased in the hippocampus. These alterations may be due to a compensatory effect of impaired insulin signaling. We demonstrated differential expression of 14-3-3 isoforms throughout brain regions of rats with IR. As a whole, our results indicate that brain 14-3-3 levels are influenced by different diets.
14-3-3蛋白家族参与广泛的细胞过程，在所有真核生物中均有表达。在哺乳动物中，已鉴定出七种亚型（β、ε、η、γ、τ、ζ和σ）。有研究表明，14-3-3蛋白可调节大脑中的胰岛素信号级联反应。本研究的目的是探讨高糖饮食诱导的胰岛素抵抗状态是否会调节大脑中14-3-3蛋白的表达。将Wistar雄性大鼠（n = 8）分为两个实验组：高糖饮食诱导的胰岛素抵抗（IR）组和对照组（CO）。130天后评估生化参数（葡萄糖耐量试验和血浆脂质谱）。解剖大脑结构（皮质和海马体）以评估不同14-3-3蛋白的信使核糖核酸（mRNA）和蛋白质水平。统计分析包括学生t检验和Pearson相关性分析。在IR组皮质中，Ywhah和Ywahq mRNA水平显著降低，而在海马体中未观察到变化。通过免疫检测发现，IR组海马体中θ亚型显著增加，而其余亚型未检测到差异。在IR组皮质中，血糖水平与Ywhah和Ywhaq mRNA水平之间呈负相关。海马体中Creb和磷脂酰肌醇3激酶（PI3K）的蛋白质水平显示增加。这些改变可能是由于胰岛素信号受损的代偿作用。我们证明了IR大鼠大脑各区域中14-3-3亚型的差异表达。总体而言，我们的结果表明，大脑中14-3-3的水平受不同饮食的影响。
