虾青素保护PC-3细胞免受H2O2氧化应激的作用机制

doi:10.7506/spkx1002-6630-201809024

食品科学 ›› 2018, Vol. 39 ›› Issue (9): 154-162.doi: 10.7506/spkx1002-6630-201809024

虾青素保护PC-3细胞免受H2O2氧化应激的作用机制

倪晓锋1，于海宁2，王姗姗1，张程程1，沈生荣1,*

1.浙江大学生物系统工程与食品科学学院，浙江杭州 310058；2.浙江工业大学药学院，浙江杭州 310014

出版日期:2018-05-15 发布日期:2018-05-15
基金资助:
浙江省医药卫生科技计划项目（2012RCA022）

Protection and Underlying Mechanism of Astaxanthin against Hydrogen Peroxide-Induced Oxidative Stress in PC-3 Cells

NI Xiaofeng1, YU Haining2, WANG Shanshan1, ZHANG Chengcheng1, SHEN Shengrong1,*

1. College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China; 2. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China

Online:2018-05-15 Published:2018-05-15

摘要/Abstract

摘要： 目的：研究虾青素对过氧化氢诱导PC-3细胞氧化应激的保护作用，探索其信号通路机制。方法：建立H2O2 氧化应激模型，采用不同浓度虾青素预处理PC-3细胞，检测细胞存活率、细胞凋亡、活性氧（reactive oxygen species， ROS）水平、B淋巴细胞瘤-2（B-cell lymphoma-2，Bcl-2）、Bcl-2相关X蛋白（Bcl-2-associated X protein，Bax）、活化半胱天冬酶-3表达及丝裂原活化蛋白激酶-核因子E2相关基因2-血红素氧合酶1（mitogen-activated protein kinases nuclear factor erythroid-2-related factor 2-heme oxygenase 1，MAPK-Nrf2-HO-1）通路的变化。结果：20 μmol/L虾青素预处理显著提高H2O2所降低的细胞存活率、降低ROS水平（P＜0.05），同时通过抑制Bcl-2/Bax比率下降及半胱天冬酶-3的激活，从而使细胞凋亡率从51.4%降低至14.8%，进一步研究发现虾青素能够促进Nrf2磷酸化，并促进 HO-1的表达，呈现浓度依赖性。通过细胞外调节蛋白激酶（extracellular regulated protein kinases，ERK）抑制剂（U0126）和Akt抑制剂（LY294002）预处理，发现当ERK和磷脂酰肌醇激酶/蛋白激酶B（phosphoinositide 3-kinase/ protein kinase B，PI3K/Akt）通路被抑制后，Nrf2表达降低，表明HO-1上调受上游ERK和胞内PI3K/Akt通路的调控。在对MAPK途径对细胞毒性影响的研究中，ERK通路被抑制后细胞存活率显著下降，而c-Jun氨基末端激酶（c-Jun N-terminal kinase，JNK）和p38 MAPK通路被抑制后并不影响其保护作用，表明虾青素抑制细胞存活率下降是通过MAPK途径中的ERK通路，而不是JNK和p38通路。结论：虾青素预处理PC-3细胞可以减轻H2O2诱导的氧化应激，维持细胞生理活性。

关键词: 虾青素, 氧化应激, PC-3细胞, 丝裂原活化蛋白激酶途径, 核因子E2相关基因2, 血红素氧合酶1

Abstract: Objective: To investigate the protective effect and underlying mechanism of astaxanthin on oxidative stress induced by hydrogen peroxide in PC-3 cells. Methods: A cellular model of oxidative stress was established by inducing PC-3 cells with H2O2, and pretreatment of PC-3 cells was conducted using astaxanthin at different concentrations. Then, the changes in cell viability, apoptosis, reactive oxygen species (ROS) levels, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 expression and the mitogen-activated protein kinases-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 (MAPK-Nrf2-HO-1) signaling pathway were investigated. Results: Astaxanthin at 20 μmol/L significantly increased cell viability, decreased the accumulation of intracellular ROS, and inhibited the decrease of Bcl-2/Bax ratio and the activation of caspase-3, consequently reducing the apoptosis rate from 51.4% to 14.8%. Our further study showed that astaxanthin could promote the phosphorylation of Nrf2 and the expression of HO-1 in a concentration dependent manner. Pretreatment with extracellular signal-regulated protein kinase (ERK) inhibitor U0126 and Akt inhibitor LY294002 decreased Nrf2 expression by inhibiting ERK and PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathways, suggesting that the up-regulation of HO-1 expression was mediated by the upstream ERK and PI3K/Akt signaling pathways. Cell viability decreased significantly when the ERK signaling pathway was inhibited, while inhibition of the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways did not affect the protective effect of astaxanthin, which demonstrated that astaxanthin could improve cell viability through the ERK signaling pathway, but not the JNK or p38 MAPK signaling pathway. Conclusion: Astaxanthin can effectively attenuate hydrogen peroxide-induced oxidative stress and maintain the normal physiological activity of PC-3 cells.

Key words: astaxanthin, oxidative stress, PC-3 cell, mitogen-activated protein kinases signaling pathway, nuclear factor erythroid-2-related factor 2, heme oxygenase 1

中图分类号:

Q291

倪晓锋，于海宁，王姗姗，张程程，沈生荣. 虾青素保护PC-3细胞免受H2O2氧化应激的作用机制[J]. 食品科学, 2018, 39(9): 154-162.

NI Xiaofeng, YU Haining, WANG Shanshan, ZHANG Chengcheng, SHEN Shengrong. Protection and Underlying Mechanism of Astaxanthin against Hydrogen Peroxide-Induced Oxidative Stress in PC-3 Cells[J]. FOOD SCIENCE, 2018, 39(9): 154-162.

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虾青素保护PC-3细胞免受H2O2氧化应激的作用机制

Protection and Underlying Mechanism of Astaxanthin against Hydrogen Peroxide-Induced Oxidative Stress in PC-3 Cells

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