Park Kang-Seo, Kim Dae-Seok, Ko Chunkyu, Lee Sang-Jin, Oh Seung Hyun, Kim Soo-Youl
Cancer Cell and Molecular Biology Branch, Goyang, Gyeonggi-do, Republic of Korea.
Front Biosci (Elite Ed). 2011 Jan 1;3(1):341-54. doi: 10.2741/e249.
Increased levels of transglutaminase 2 (TGase 2) expression have been reported in many inflammatory diseases, as well as in drug resistant cancer cells. Previous reports have shown that TGase 2 is capable of inducing nuclear factor-kappaB (NF-kappaB) activation via depletion of inhibitor of kappaB (I-kappaB)alpha through polymerization in the absence of I-kappaBalpha kinase activation. This raises the question of whether increased expression of TGase 2 can extend NF-kappaB activation mediated by a canonical activation pathway. In the TGase 2-inducible EcR23/TG cell line, TGase 2 over-expression resulted in sustained activation of NF-kappa B in the presence of TNF-alpha, for up to 24 hrs, while in the absence of TGase 2 induction, NF-kappaB activity was restored to basal levels within 6 hrs of TNF-alpha treatment. In mice injected with an adenovirus vector expressing TGase 2, NF-kappaB was constitutively activated for up to 5 days, whereas Adeno/GFP-injected mice exhibited attenuated activation of NF-kappaB in response to TNF-alpha stress. Thus, the presence of increased levels of TGase 2 may exacerbate NF-kappa B activation in inflammatory states.
据报道，在许多炎症性疾病以及耐药癌细胞中，转谷氨酰胺酶2（TGase 2）的表达水平会升高。先前的报道表明，在缺乏I-κBα激酶激活的情况下，TGase 2能够通过I-κBα的聚合消耗来诱导核因子-κB（NF-κB）激活。这就提出了一个问题，即TGase 2表达的增加是否能延长由经典激活途径介导的NF-κB激活。在TGase 2诱导型EcR23/TG细胞系中，TGase 2过表达导致在存在肿瘤坏死因子-α（TNF-α）的情况下，NF-κB持续激活长达24小时，而在没有TGase 2诱导的情况下，TNF-α处理6小时内NF-κB活性恢复到基础水平。在注射了表达TGase 2的腺病毒载体的小鼠中，NF-κB持续激活长达5天，而注射腺病毒/绿色荧光蛋白（Adeno/GFP）的小鼠在受到TNF-α应激时NF-κB的激活减弱。因此，TGase 2水平升高可能会加剧炎症状态下的NF-κB激活。
