An investigation of the developmental neurotoxic potential of curcumol in PC12 cells

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2016-11-06 DOI:10.1080/15376516.2016.1207735

Chunlei Yu, Xiaojie Sun, Y. Niu

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引用次数: 8

Abstract

Abstract Curcuma phaeocaulis Val. is a Chinese medicinal herb that is contraindicated during pregnancy for over a thousand years in China. The aims of the present study were to evaluate the effect of curcumol (one of the major components of C. phaeocaulis Val.) on neurite outgrowth and characterize the signal transduction pathways in PC12 cells. Curcumol significantly inhibited neurite outgrowth and cell proliferation, but did not cause cell death at a concentration of 450 μM in differentiated PC12 cells. In addition, curcumol evoked oxidative stress and it was indicated by an elevation in reactive oxygen species (ROS) and lipid peroxidation (LPO). Although PC12 cells exhibited inhibition of the differentiation into the acetylcholine (ACh) phenotype following 450 μM curcumol exposure, there was no significant alteration in net shift toward the ACh phenotype or tyrosine hydroxylase (TH) phenotype was observed. Neural cell adhesion molecule (NCAM)/focal adhesion kinase (FAK) but not extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling was repressed by curcumol exposure in differentiated PC12 cells. Curcumol does not affect calpain activity and nuclear factor-κB (NF-κB) DNA-binding activity. These findings suggest that curcumol might be a developmental neurotoxicant and NCAM/FAK signaling pathway may play an important role in curcumol-evoked inhibition of neurite outgrowth.

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姜黄酚对PC12细胞发育神经毒性的研究

姜黄(Curcuma phaeocaulis valis)是一种在中国有一千多年历史的孕期禁忌中药。本研究的目的是评估姜黄酚(C. phaeocaulis Val.的主要成分之一)对PC12细胞神经突生长的影响，并表征其信号转导途径。Curcumol在450 μM浓度下显著抑制PC12分化细胞的神经突生长和细胞增殖，但未引起细胞死亡。此外，姜黄酚还能引起氧化应激，并通过提高活性氧(ROS)和脂质过氧化(LPO)来证明。虽然在450 μM莪术醇暴露后，PC12细胞表现出向乙酰胆碱(ACh)表型分化的抑制，但没有观察到向ACh表型或酪氨酸羟化酶(TH)表型净转移的显著改变。在分化的PC12细胞中，姜黄酚暴露可抑制神经细胞粘附分子(NCAM)/局灶粘附激酶(FAK)信号，但不抑制细胞外信号调节激酶1和2 (ERK1/2)信号。姜黄酚不影响钙蛋白酶活性和核因子-κB (NF-κB) dna结合活性。这些发现提示姜黄醇可能是一种发育性神经毒物，NCAM/FAK信号通路可能在姜黄醇诱发的神经突生长抑制中起重要作用。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.