Weech Michelle, Quash Michelle, Walters Eric
Department of Biochemistry and Molecular Biology, Howard University, College of Medicine, Washington, DC 20059, USA.
J Neurosci Res. 2003 Sep 1;73(5):679-85. doi: 10.1002/jnr.10687.
The acute phase response (APR) has been shown to alter expression and activity of biotransformation enzymes, such as the phase I cytochromes p450 and phase II glutathione S-transferases (GSTs). The cytochromes p450 and GSTs are expressed abundantly and colocalized to non-neuronal cells of the olfactory mucosa. Previous studies indicate that olfactory cytochromes p450 expression and activity is altered during periods of localized inflammation and infection. Little is understood, however, about the influence of the APR on olfactory GST enzymes. This study investigated effects of the APR on olfactory GST isozymes expression and activity in mouse olfactory mucosa after 24-hr treatment with the acute phase inducer, polyinosinic: polycytidylic acid (polyIC). Western blot analysis using antibodies directed against specific GST isoforms alpha (A1-1), micro (M1-1), and pi (P1-1) demonstrated that their expression was unaltered by polyIC treatment. In contrast, olfactory p450 2E1 expression was significantly decreased. Enzymatic activity of the olfactory GSTs toward the general substrate, 1-chloro-2,4-dinitrobenzene (CDNB) was unchanged during the APR. Analysis of olfactory glutathione content during the APR showed that it was also unaffected by polyIC. The insensitivity of these olfactory GST isoforms during the APR may play a significant role toward limiting the impact of infection and inflammation on the olfactory system.
急性期反应(APR)已被证明会改变生物转化酶的表达和活性,如I相细胞色素P450和II相谷胱甘肽S-转移酶(GSTs)。细胞色素P450和GSTs大量表达,并定位于嗅黏膜的非神经细胞。先前的研究表明,在局部炎症和感染期间,嗅觉细胞色素P450的表达和活性会发生改变。然而,关于APR对嗅觉GST酶的影响知之甚少。本研究调查了用急性期诱导剂聚肌苷酸:聚胞苷酸(polyIC)处理24小时后,APR对小鼠嗅黏膜中嗅觉GST同工酶表达和活性的影响。使用针对特定GST同工型α(A1-1)、μ(M1-1)和π(P1-1)的抗体进行蛋白质印迹分析表明,它们的表达不受polyIC处理的影响。相比之下,嗅觉P450 2E1的表达显著降低。在急性期反应期间,嗅觉GSTs对一般底物1-氯-2,4-二硝基苯(CDNB)的酶活性没有变化。对急性期反应期间嗅黏膜中谷胱甘肽含量的分析表明,它也不受polyIC的影响。这些嗅觉GST同工型在急性期反应期间的不敏感性可能对限制感染和炎症对嗅觉系统的影响起重要作用。