D-Limonene protects PC12 cells against corticosterone-induced neurotoxicity by activating the AMPK pathway
D-Limonene protects PC12 cells against corticosterone-induced neurotoxicity by activating the AMPK pathway
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D-柠檬烯通过激活 AMPK 途径保护 PC12 细胞免受皮质酮诱导的神经毒性
DOI：
10.1016/j.etap.2019.05.001
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发表时间：
2019-08-01
影响因子：
4.3
通讯作者：
Weng, Lian-Jin
中科院分区：
文献类型：
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作者：
Tang, Xue-ping;Guo, Xiao-hua;Weng, Lian-Jin
应激诱导的激素皮质酮引发氧化应激和炎症反应，最终导致细胞凋亡和神经系统变化。我们评估了D-柠檬烯对皮质酮诱导的神经毒性的PC 12细胞模型的影响，以及这些影响是否涉及AMP激活的蛋白激酶（AMPK α）通路。用皮质酮与或不与D-柠檬烯处理PC 12细胞24小时。进行蛋白质印迹以测量AMPK通路成员[沉默交配型信息调节2同源物-1（SIRT 1）、AMPK α和核因子（NF κ B）]、活性氧类、炎性细胞因子和细胞凋亡标志物的活化。末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）用于测量处理后的细胞死亡。D-柠檬烯逆转皮质酮对PC 12细胞的作用：降低丙二醛（MDA）和一氧化氮（NO）含量，降低NADPH氧化酶活性（p67-phox和p47-phox）、促炎标志物[诱导型一氧化氮合酶（iNOS）、环氧合酶-2（考克斯-2）、白细胞介素6（IL-6）、白细胞介素1 β（IL-1 β）]的表达（IL-1 β）和肿瘤坏死因子α（TNF-α）]和促凋亡蛋白[Bcl 2与X蛋白（Bax）和裂解的半胱天冬酶-3）的表达。D-柠檬烯还增加了抗氧化酶超氧化物歧化酶1（SOD 1）和血红素加氧酶1（HO-1）以及抗凋亡蛋白Bcl-2的水平，同时减少了TUNEL阳性细胞的数量。二柠檬烯显著激活AMPK α，并通过上调SIRT 1抑制NF-κ B B核转位。添加化合物C，AMPK抑制剂，严重削弱了D-柠檬烯的这些神经保护作用。D-柠檬烯对皮质酮诱导的PC 12细胞损伤具有神经保护作用，其通过激活AMPK α信号通路诱导，从而抑制活性氧和炎症因子。这些数据表明，D-柠檬烯可以防止神经元死亡，改善抑郁症状。
The stress-induced hormone corticosterone initiates oxidative stress and inflammatory responses, culminating in cell apoptosis and neurological changes. We assessed the effects of D-Limonene on a PC12 cellular model of corticosterone-induced neurotoxicity, and whether these effects involved the AMP-activated protein kinase (AMPK alpha) pathway. PC12 cells were treated with corticosterone with or without D-limonene for 24 h. Western blots were performed to measure activation of AMPK pathway members [Silent mating type information regulation 2 homolog-1 (SIRT1), AMPK alpha, and nuclear factor (NF kappa B)], reactive oxygen species, inflammatory cytokines, and markers of apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was used to measure cell death after treatment. D-Limonene reversed the effects of corticosterone on PC12 cells: it decreased the levels of malondialdehyde (MDA) and nitric oxide (NO), activities of NADPH oxidase (p67-phox and p47-phox), expression of pro-inflammatory markers [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha)], and expression of pro-apoptotic proteins [Bcl2 associated with X protein (Bax) and cleaved caspase-3)]. D-Limonene also increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO-1) and the anti-apoptotic protein Bcl-2 while decreasing the number of TUNEL-positive cells. Dlimonene significantly activated AMPK alpha and suppressed NF-kappa B nuclear translocation through up-regulation of SIRT1. Addition of compound C, an AMPK inhibitor, severely weakened these neuroprotective effects of D-limonene. D-Limonene has a neuroprotective effect on corticosterone-induced PC12 cell injury induced by activating the AMPK alpha signaling pathway, and thereby inhibiting reactive oxygen species and inflammatory factors. These data suggest that D-limonene might protect against neuronal death to improve depressive symptoms.