ABSTRACT

Local action of nicotine on oral mucosa contributes to the pathogenesis of precancerous and cancerous lesions. Nicotine participation in the mechanism of apoptosis in normal mucosa has not been established. Peroxiredoxin 1 (Prx1) is a cellular antioxidant that participates in regulating apoptosis. We investigated expression of Prx1 and proteins in apoptosis-related downstream signaling by mitogen-activated protein kinases (MAPKs) in nicotine-treated tongue tissues of wild-type and Prx1 knockout (Prx1^±) mice; we also investigated these processes in mouse embryonic fibroblast (MEF) cells in vitro. Nicotine increased the expression of Prx1 mRNA in tongue tissues in vivo. The rate of apoptosis was similar among the nicotine-treated mice, nicotine-treated + Prx1^± mice and untreated controls. The expression of p-JNK was greater in Prx1^± mice compared to control mice. In MEF cells, nicotine increased the expression of Prx1 and inhibited apoptosis and expression of p-p38 and p-JNK. Prx1 knockdown animals exhibited increased apoptotic rate and expression of p-p38 and p-JNK in MEFs. Nicotine-regulated apoptosis might occur via a Prx1-dependent pathway.

摘要

尼古丁对口腔粘膜的局部作用有助于癌前病变和癌性病变的发病机理。尚未确定尼古丁参与正常粘膜细胞凋亡的机制。Peroxiredoxin 1（Prx1）是一种细胞抗氧化剂，参与调节细胞凋亡。我们调查了在野生型和Prx1基因敲除（Prx1 ^±）小鼠的尼古丁治疗的舌头组织中，丝裂素激活的蛋白激酶（MAPK）对细胞凋亡相关下游信号的表达中Prx1和蛋白的表达；我们还研究了体外小鼠胚胎成纤维细胞（MEF）中的这些过程。尼古丁增加了体内舌组织中Prx1 mRNA的表达。尼古丁治疗组小鼠的凋亡率相似，尼古丁治疗组+ Prx1 ^±小鼠和未经处理的对照。与对照小鼠相比，Prx1 ^±小鼠中p-JNK的表达更高。在MEF细胞中，尼古丁增加Prx1的表达，并抑制细胞凋亡以及p-p38和p-JNK的表达。Prx1组合式动物在MEF中显示出较高的凋亡率以及p-p38和p-JNK的表达。尼古丁调节的细胞凋亡可能通过Prx1依赖性途径发生。