Feola Julianne, Barton Alan, Akbar Abdullah, Keillor Jeffrey, Johnson Gail V W
Department of Neuroscience, University of Rochester Medical Center, 601 Elmwood Ave, Box 603, Rochester, NY 14642, United States.
Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Ave, Box 604, Rochester, NY 14642, United States.
Brain Res. 2017 Aug 1;1668:1-11. doi: 10.1016/j.brainres.2017.05.009. Epub 2017 May 15.
Transglutaminase 2 (TG2) is a multifunctional protein that can contribute to cell death and cell survival processes in a variety of disease contexts. Within the brain, TG2 has been shown to promote cell death in ischemic injury when expressed in astrocytes (Colak and Johnson, 2012). However, the specific functions and characteristics of astrocytic TG2 that mediate this effect are largely unknown. Therefore, the goal of this study was to investigate the role of astrocytic TG2 in mediating cellular viability processes in the context of ischemic injury, with a specific focus on its contributions to intracellular signaling cascades. We show that, in response to oxygen/glucose deprivation (OGD), acute lentiviral-mediated knockdown of TG2, as well as inhibition with an irreversible TG2 inhibitor, enhances cell survival. We also show that TG2 depletion increases nuclear factor-κB (NF-κB) signaling, whereas inhibition reduces NF-κB activity. Despite its clear contribution to NF-κB signaling, however, TG2 modulation of NF-κB signaling is not likely to be a major contributor to its ability to mediate astrocytic viability in this context. Overall, the results of this study provide insight into the role of TG2 in astrocytes and suggest possible avenues for future study of the relationship between astrocytic TG2 and ischemic injury.
转谷氨酰胺酶2（TG2）是一种多功能蛋白质，在多种疾病背景下可参与细胞死亡和细胞存活过程。在大脑中，已表明当TG2在星形胶质细胞中表达时，它会在缺血性损伤中促进细胞死亡（科拉克和约翰逊，2012年）。然而，介导这种效应的星形胶质细胞TG2的具体功能和特性在很大程度上尚不清楚。因此，本研究的目的是探讨星形胶质细胞TG2在缺血性损伤背景下介导细胞存活过程中的作用，特别关注其对细胞内信号级联反应的贡献。我们发现，在氧/葡萄糖剥夺（OGD）反应中，急性慢病毒介导的TG2敲低以及用不可逆的TG2抑制剂进行抑制，均可提高细胞存活率。我们还表明，TG2的缺失会增加核因子κB（NF-κB）信号传导，而抑制作用则会降低NF-κB活性。然而，尽管TG2对NF-κB信号传导有明确贡献，但在这种情况下，TG2对NF-κB信号传导的调节不太可能是其介导星形胶质细胞存活能力的主要因素。总体而言，本研究结果深入了解了TG2在星形胶质细胞中的作用，并为未来研究星形胶质细胞TG2与缺血性损伤之间的关系提供了可能的途径。
