Istanbul University, Faculty of Science, Department of Biology, Istanbul University, Istanbul, Turkey.
J Cell Biochem. 2018 Feb;119(2):2048-2060. doi: 10.1002/jcb.26367. Epub 2017 Sep 18.
In this study, it was aimed to determine the doses of 4-methylcatechol causing cell death in rat insulinoma β-cells (INS-1), to find out the type of cellular death at these doses, and to investigate the molecular mechanism of cellular death occurring. More necrotic cells were observed than apoptosis with the administration of 350, 400, and 450 μM 4-methylcatechol. Lactate dehydrogenase levels, reactive oxygen species, mitochondrial potential loss, ATP, and GTP losses increased at these doses. The JNK and ERK cellular pathway were screened. We observed an increase in p-RAF1 activity, the active JNK amount, the total c-Jun amount, while a decrease in p-RAF1 expression, the total JNK amount, JNK expression, ATF2 expression, active ERK, and its expression and Elk1 expression. It was concluded that cells perform necrotic death by the following options: i) phosphorylated RAF1 activates the JNK pathway with the activity of transcription factor c-Jun; ii) Hsp 70 and Hsp 90 do not show a change inside the cell, rendering the JNK pathway active.
在这项研究中，目的是确定 4-甲基儿茶酚引起大鼠胰岛素瘤β细胞（INS-1）细胞死亡的剂量，确定这些剂量下的细胞死亡类型，并研究发生细胞死亡的分子机制。与给予 350、400 和 450μM 4-甲基儿茶酚相比，观察到更多的坏死细胞而不是凋亡细胞。这些剂量下乳酸脱氢酶水平、活性氧、线粒体势能丧失、ATP 和 GTP 丢失增加。筛选了 JNK 和 ERK 细胞途径。我们观察到 p-RAF1 活性、活性 JNK 量、总 c-Jun 量增加，而 p-RAF1 表达、总 JNK 量、JNK 表达、ATF2 表达、活性 ERK 及其表达和 Elk1 表达减少。结论是细胞通过以下选项发生坏死性死亡：i）磷酸化 RAF1 通过转录因子 c-Jun 的活性激活 JNK 途径；ii）细胞内的 Hsp 70 和 Hsp 90 没有变化，使 JNK 途径活跃。
