Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Neurosci Res. 2012 Apr;72(4):289-95. doi: 10.1016/j.neures.2011.12.008. Epub 2011 Dec 24.
Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and differentiation processes, plays a modulatory role in the cell response to stressors. Herein, we used olfactory ensheathing cells (OECs), representing an unusual population of glial cells to promote axonal regeneration and to provide trophic support, as well as to assess whether the effect of some Growth Factors (GFs), NGF, bFGF or GDNF, on TG2 overexpression induced by stress conditions, such as glutamate or lipopolysaccaride (LPS). Glial Fibrillary Acidic Protein (GFAP) and vimentin were used as markers of astroglial differentiation and cytoskeleton component, respectively. Glutamate or LPS treatment induced a particular increase of TG2 expression. A pre-treatment of the cells with the GFs restored the levels of the protein to that of untreated ones. Our results demonstrate that the treatment of OECs with the GFs was able to restore the OECs oxidative status as modified by stress, also counteracting TG2 overexpression. It suggests that, in OECs, TG2 modulation or inhibition induced by GFs might represent a therapeutic target to control the excitotoxicity and/or inflammation, which are involved in several acute and chronic brain diseases.
组织转谷氨酰胺酶（TG2）是一种多功能酶，参与细胞增殖和分化过程，在细胞对应激原的反应中起调节作用。在此，我们使用嗅鞘细胞（OECs），作为一种促进轴突再生和提供营养支持的独特的神经胶质细胞，来评估一些生长因子（GFs），如神经生长因子（NGF）、碱性成纤维细胞生长因子（bFGF）或胶质细胞源性神经营养因子（GDNF），对由谷氨酸或脂多糖（LPS）等应激条件诱导的 TG2 过表达的影响。神经胶质酸性蛋白（GFAP）和波形蛋白分别作为星形胶质细胞分化和细胞骨架成分的标志物。谷氨酸或 LPS 处理诱导 TG2 表达的特定增加。细胞用 GFs 预处理可将蛋白质水平恢复到未处理的水平。我们的结果表明，GFs 处理 OECs 能够恢复由应激引起的 OECs 氧化状态，同时还能抑制 TG2 的过表达。这表明，在 OECs 中，由 GFs 诱导的 TG2 调节或抑制可能代表一种治疗靶点，以控制与几种急性和慢性脑疾病相关的兴奋性毒性和/或炎症。
