Perfluorooctanoic acid-induced cell death via the dual roles of ROS-MAPK/ERK signaling in ameloblast-lineage cells.
Perfluorooctanoic acid-induced cell death via the dual roles of ROS-MAPK/ERK signaling in ameloblast-lineage cells.
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DOI：
10.1016/j.ecoenv.2023.115089
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发表时间：
2023-07-15
影响因子：
6.8
通讯作者：
Suzuki, Maiko
中科院分区：
文献类型：
--
作者：
Fujiwara, Natsumi;Yamashita, Shohei;Okamoto, Motoki;Cooley, Marion A.;Ozaki, Kazumi;Everett, Eric T.;Suzuki, Maiko
全氟辛酸（PFOA）是一种人造氟化有机化合物，由于其潜在的健康危害而引起了公众越来越多的关注。不安全水平的 PFOA 暴露会影响生殖、生长和发育。在牙釉质发育（釉质生成）过程中，包括氟化物在内的环境因素会导致牙釉质发育不全。然而，PFOA 对成釉细胞和牙釉质形成的影响仍然很大程度上未知。在本研究中，我们展示了几种 PFOA 介导的细胞死亡途径（坏死/坏死性凋亡和细胞凋亡），并评估了 ROS-MAPK/ERK 信号在 PFOA 介导的小鼠成釉细胞谱系细胞 (ALC) 细胞死亡中的作用。 ALC 细胞用 PFOA 处理。分别通过MTT测定和集落形成测定分析细胞增殖和活力。 PFOA 以剂量依赖性方式抑制细胞增殖和活力。 PFOA 诱导坏死（PI 阳性细胞）和细胞凋亡（cleaved-caspase-3、γH2AX 和 TUNEL 阳性细胞）。 PFOA 显着增加 ROS 产生并上调磷酸-(p)-ERK。与单独使用 PFOA 相比，添加 ROS 抑制剂 N-乙酰半胱氨酸 (NAC) 可抑制 p-ERK 并减少坏死，并增加细胞活力，但 NAC 不会改变细胞凋亡。这表明PFOA介导的坏死是由ROS-MAPK/ERK信号传导诱导的，但细胞凋亡与ROS无关。与单独使用 PFOA 相比，添加 MAPK/ERK 抑制剂 PD98059 可抑制坏死并增加细胞活力。有趣的是，PD98059 增强了 PFOA 介导的细胞凋亡。这表明p-ERK促进坏死但抑制细胞凋亡。与单独使用 PFOA 相比，添加坏死性凋亡抑制剂 Necrostatin-1 可恢复细胞活力，而 pancaspase 抑制剂 Z-VAD 并不能减轻 PFOA 介导的细胞死亡。这些结果表明1）PFOA介导的细胞死亡主要是由ROS-MAPK/ERK信号传导引起的坏死/坏死性凋亡而不是细胞凋亡引起的，2）MAPK/ERK信号在PFOA处理下发挥双重作用（促进坏死和抑制细胞凋亡）。这是首次报告表明 PFOA 可能被认为是隐源性牙釉质畸形的可能致病因素。需要进一步的研究来阐明 PFOA 介导的对牙釉质生成不利影响的机制。
Perfluorooctanoic acid (PFOA) is an artificial fluorinated organic compound that has generated increased public attention due to its potential health hazards. Unsafe levels of PFOA exposure can affect reproduction, growth and development. During tooth enamel development (amelogenesis), environmental factors including fluoride can cause enamel hypoplasia. However, the effects of PFOA on ameloblasts and tooth enamel formation remain largely unknown. In the present study we demonstrate several PFOA-mediated cell death pathways (necrosis/necroptosis, and apoptosis) and assess the roles of ROS-MAPK/ERK signaling in PFOA-mediated cell death in mouse ameloblast-lineage cells (ALC). ALC cells were treated with PFOA. Cell proliferation and viability were analyzed by MTT assays and colony formation assays, respectively. PFOA suppressed cell proliferation and viability in a dose dependent manner. PFOA induced both necrosis (PI-positive cells) and apoptosis (cleaved-caspase-3, γH2AX and TUNEL-positive cells). PFOA significantly increased ROS production and up-regulated phosphor-(p)-ERK. Addition of ROS inhibitor N-acetyl cysteine (NAC) suppressed p-ERK and decreased necrosis, and increased cell viability compared to PFOA alone, whereas NAC did not change apoptosis. This suggests that PFOA-mediated necrosis was induced by ROS-MAPK/ERK signaling, but apoptosis was not associated with ROS. Addition of MAPK/ERK inhibitor PD98059 suppressed necrosis and increased cell viability compared to PFOA alone. Intriguingly, PD98059 augmented PFOA-mediated apoptosis. This suggests that p-ERK promoted necrosis but suppressed apoptosis. Addition of the necroptosis inhibitor Necrostatin-1 restored cell viability compared to PFOA alone, while pancaspase inhibitor Z-VAD did not mitigate PFOA-mediated cell death. These results suggest that 1) PFOA-mediated cell death was mainly caused by necrosis/necroptosis by ROS-MAPK/ERK signaling rather than apoptosis, 2) MAPK/ERK signaling plays the dual roles (promoting necrosis and suppressing apoptosis) under PFOA treatment. This is the initial report to indicate that PFOA could be considered as a possible causative factor for cryptogenic enamel malformation. Further studies are required to elucidate the mechanisms of PFOA-mediated adverse effects on amelogenesis.
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组蛋白乙酰转移酶促进LS8细胞中的氟化物毒性。
影响因子：
8.8
作者：
Deng H;Fujiwara N;Cui H;Whitford GM;Bartlett JD;Suzuki M
通讯作者：
Suzuki M
影响因子：
--
作者：
Mukerji P;Rae JC;Buck RC;O'Connor JC
通讯作者：
O'Connor JC
影响因子：
9.3
作者：
Melo-Lima, Sara;Lopes, Maria C.;Mollinedo, Faustino
通讯作者：
Mollinedo, Faustino
DOI：
10.1016/j.aquatox.2016.03.026
发表时间：
2016-06
期刊：
Aquatic toxicology (Amsterdam, Netherlands)
影响因子：
--
作者：
Jantzen CE;Annunziato KA;Bugel SM;Cooper KR
通讯作者：
Cooper KR
影响因子：
5.6
作者：
Mokra K
通讯作者：
Mokra K