甲醛对HepG2细胞游离胆固醇代谢的影响

doi:10.3969/j.issn.1004-616x.2019.01.006

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (1): 35-40.doi: 10.3969/j.issn.1004-616x.2019.01.006

甲醛对HepG2细胞游离胆固醇代谢的影响

姜雪霞, 王盼, 刘艳飞, 张艳, 白剑英

山西医科大学公共卫生学院环卫教研室, 山西太原 030001

收稿日期:2018-10-15 修回日期:2018-12-12 出版日期:2019-01-31 发布日期:2019-01-31
通讯作者: 白剑英,E-mail:jybai66@aliyun.com E-mail:jybai66@aliyun.com
作者简介:姜雪霞,E-mail:1170052620@qq.com。
基金资助:
山西省留学回国人员科研资助项目（2014-034）；山西省自然科学基金项目（201701D121140）

Effects of formaldehyde on free cholesterol metabolism in HepG2 cells

JIANG Xuexia, WANG Pan, LIU Yanfei, ZHANG Yan, BAI Jianying

Department of Environment Health, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China

Received:2018-10-15 Revised:2018-12-12 Online:2019-01-31 Published:2019-01-31

摘要/Abstract

摘要： 目的：研究甲醛（FA）对人肝癌细胞株HepG2细胞游离胆固醇（FC）含量的影响及其作用机制。方法：分别采用0.004、0.02、0.1 mmol/L FA处理人肝癌细胞株HepG2细胞24和48 h，以完全培养基为阴性对照，过氧化物酶法测定HepG2细胞内FC含量；采用Western blot法检测HepG2细胞固醇调节元件结合蛋白-2（SREBP-2）、羟甲基戊二酸单酰辅酶A还原酶（HMGCR）、胆固醇酰基转移酶（ACAT）和低密度脂蛋白受体（LDLR）的蛋白表达水平。结果：与阴性对照组相比，各浓度的FA染毒24 h或0.02和0.1 mmol/L FA染毒48 h后，HepG2细胞内FC含量均明显增加（P均 < 0.05）；FA染毒24和48 h后细胞内HMGCR蛋白表达水平均明显增加（P < 0.05）；FA染毒24 h后，ACAT和LDLR表达水平均明显降低（P均 < 0.05）；FA染毒48 h，LDLR蛋白表达水平明显降低（P < 0.05），ACAT蛋白表达水平在0.02和0.1 mmol/L FA组明显降低（P < 0.05）。结论：甲醛染毒可使HepG2细胞内FC含量增加，可能与胆固醇的从头合成增加和胆固醇酯化水平降低有关。

关键词: 甲醛, 固醇调节元件结合蛋白2, 羟甲基戊二酸单酰辅酶A还原酶, 胆固醇酰基转移酶, 低密度脂蛋白受体

Abstract: OBJECTIVE:To explore effects of formaldehyde (FA) on intra-hepatocellular free cholesterol content in HepG2 cells. METHODS:HepG2 cells were treated with formaldehyde at 0.004,0.02 and 0.1 mmol/L concentrations for 24 and 48 hours,respectively. The content of intra-hepatocellular free cholesterol was detected by using free the cholesterol GPO-POD assay kit. Western blot was used to detect protein expression of the sterol regulatory element-binding protein (SREBP) -2,hydroxy mothylglutaryl coenzyme A reductase (HMGCR),acyl coenzyme A-cholesterol acyltransferase (ACAT) and low-density lipoprotein receptor (LDLR). RESULTS:Compared with negative control,the contents of intra-hepatocellular FC were increased significantly after treatments with FA for 24 h and 0.02 and 0.1 mmol/L for 48 h (P < 0.05). HMGCR expression levels were significantly increased after exposure to formaldehyde for 24 and 48 h (P < 0.05). After treatment with FA for 24 h,expression levels of ACAT and LDLR were significantly down-regulated (P < 0.05). After 48 h,expression levels of LDLR were decreased significantly,whereas the levels of ACAT were decreased significantly after treatment with 0.02 and 0.1 mmol/L FA (P < 0.05). CONCLUSION:FA exposure increased intra-hepatocellular free cholesterol contents in HepG2 cells. The increase could be caused by elevated de novo synthesis of cholesterol and decreased cholesterol esterification.

Key words: formaldehyde, sterol regulatory element binding protein 2, hydroxy mothylglutaryl coenzyme A reductase, acyl coenzyme A-cholesterol acyltransferase, low-density lipoprotein receptor

中图分类号:

R114

姜雪霞, 王盼, 刘艳飞, 张艳, 白剑英. 甲醛对HepG2细胞游离胆固醇代谢的影响[J]. 癌变·畸变·突变, 2019, 31(1): 35-40.

JIANG Xuexia, WANG Pan, LIU Yanfei, ZHANG Yan, BAI Jianying. Effects of formaldehyde on free cholesterol metabolism in HepG2 cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(1): 35-40.

参考文献

[1] 于颐光,王瑞.甲醛暴露的健康危害[J]. 预防医学论坛,2015,21(2):130-136.
[2] KIM K H,JAHAN S A,LEE J T. Exposure to formaldehyde and its potential human health hazards[J]. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev,2011,29(4):277-299.
[3] SAITO Y,NISHIO K,YOSHIDA Y,et al. Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species[J]. Toxicology,2005,210(2/3):235-245.
[4] 张艺滨,吴传楠,杨慧敏,等. 甲醛毒性作用的研究进展[J]. 吉林医药学院学报,2008,29(4):232-235.
[5] HIDIR P,NERIMAN C C,DSMAIL Z,et al. The effect of melatonin hormone on formaldehyde-induced liver injury:A light microscopic and biochemical study[J]. Firat Tip Dergisi,2008,13(2):92-97.
[6] KU R H,BILLINGS R E. Relationships between formaldehyde metabolism and toxicity and glutathione concentrations in isolated rat hepatocytes[J]. Chem Biol Interact,1984,51(1):25-36.
[7] 王凤玲,隋小芳,索树珍,等. 胆固醇代谢紊乱及其相关疾病的研究进展[J]. 中国老年保健医学,2015,13(1):13-15.
[8] MUSSO G,GAMBINO R,CASSADER M. Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis[J]. Prog Lipid Res,2013,52(1):175-191.
[9] KERR T A,DAVIDSON N O. Cholesterol and NAFLD:Renewed focus on an old villain[J]. Hepatology,2012,56(5):1995-1998.
[10] BAI J Y,WANG P,LIU Y F,et al. Formaldehyde alters triglyceride synthesis and very low-density lipoprotein secretion in a time-dependent manner[J]. Environ Toxicol Pharmacol,2017,56:15-20.
[11] 郑健. 甲醛与人体健康[J]. 大学化学,2009,24(1):52-56.
[12] BAAN R,GROSSE Y,STRAIF K,et al. A review of human carcinogens-part F:chemical agents and related occupations[J]. Lancet Oncol,2009,10(12):1143-1144.
[13] TENG S,BEARD K,POURAHMAD J,et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes[J]. Chem Biol Interact,2001,130/132(1/2/3):285-296.
[14] 薛来俊,晓开提·依不拉音,张彦红.甲醛染毒小鼠肝脏,肾脏,脾脏的病理变化[J]. 中国职业医学,2007,34(3):197-198.
[15] NAKAMUTA M,FUJINO T,YADA R,et al. Impact of cholesterol metabolism and the LXRalpha-SREBP-1c pathway on nonalcoholic fatty liver disease[J]. Int J Mol Med,2009,23(5):603-608.
[16] WANG X H,TIAN Y,GUO Z J,et al. Cholesterol metabolism and expression of its relevant genes in cultured steatotic hepatocytes[J]. J Dig Dis,10(4):310-314.
[17] DENG X,PAN X,CHENG C,et al. Regulation of SREBP-2 intracellular trafficking improves impaired autophagic flux and alleviates endoplasmic reticulum stress in NAFLD[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2016,1862(3):337-350.
[18] KRYCER J R,PHAN L,BROWN R J. A key regulator of cholesterol homoeostasis,SREBP-2,can be targeted in prostate cancer cells with natural products[J]. Biochem J,2012,446(2):191-201.
[19] NESS G C,CHAMBERS C M. Feedback and hormonal regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase:the concept of cholesterol buffering capacity[J]. Proc Soc Exp Biol Med,2000,224(1):8-19.
[20] BROWN M S,GOLDSTEIN J L,BROWN M S,et al. Multivalent feedback regulation of HMG CoA reductase,a control mechanism coordinating isoprenoid synthesis and cell growth[J]. J Lipid Res,1980,21(5):505-517.
[21] REYNOLDS G A,GOLDSTEIN J L,BROWN M S. Multiple mRNAs for 3-hydroxy-3-methylglutaryl coenzyme A reductase determined by multiple transcription initiation sites and intron splicing sites in the 5'-untranslated region[J]. J Biol Chem,1985,260(18):10369-10377.
[22] SHIMANO H,HORTON J D,HAMMER R E,et al. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a[J]. J Clin Invest,1996,98(7):1575-1584.
[23] 王晓微,高明明. 酯酰辅酶A:胆固醇酰基转移酶的研究进展[J]. 中国动脉硬化杂志,2018,26(7):685-690.
[24] STOUDT,G. Cell toxicity induced by inhibition of acyl coenzyme A:Cholesterol acyltransferase and accumulation of unesterified cholesterol[J]. J Biol Chem,1995,270(11):5772-5778.
[25] YAMASHITA M,KUMAZOE M,NAKAMURA Y,et al. The Combination of green tea extract and eriodictyol inhibited high-fat/high-sucrose diet-induced cholesterol upregulation is accompanied by suppression of cholesterol synthesis enzymes[J]. J Nutr Sci Vitaminol,2016,62(4):249-256.
[26] GO G,MANI A. Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis[J]. Yale J Biol Med,2012,85(1):19-28.
[27] 金文媛,赵正言. 低密度脂蛋白受体与代谢综合征的相关性研究进展[J]. 浙江大学学报(医学版),2015,44(1):101-107.

甲醛对HepG2细胞游离胆固醇代谢的影响

Effects of formaldehyde on free cholesterol metabolism in HepG2 cells

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 12

编辑推荐

Metrics

本文评价

[1]	张超, 白剑英, 王东新, 闫丹丹, 王盼, 刘艳飞. 甲醛对人肝癌细胞株HepG2内质网应激相关Bip和CANX mRNA及蛋白表达水平的影响[J]. 癌变·畸变·突变, 2017, 29(5): 340-345,351.
[2]	王超, 段链, 张宏伟. 汞、砷、甲醛单一及复合污染对蚕豆根尖细胞微核的影响及污染评价[J]. 癌变·畸变·突变, 2016, 28(5): 383-387.
[3]	柯跃斌，黄娟，朱舟，吴双，陶功华. 甲醛对人Ⅱ型肺泡上皮细胞DNA氧化和甲基化水平的影响[J]. 癌变·畸变·突变, 2014, 26(1): 25-29.
[4]	闫丹丹,白剑英,梁瑞峰,王幼萍,雷佩玉. 甲醛对HepG2细胞脂肪代谢的影响[J]. 癌变·畸变·突变, 2013, 25(6): 416-421.
[5]	张喆,袁衡,朱武,黄河,罗晓敏. 甲醛和苯联合染毒对小鼠胚胎的影响[J]. 癌变·畸变·突变, 2013, 25(5): 369-372.
[6]	张　娟(综述),浦跃朴(审校). 苯和甲醛装修污染与白血病发病风险的研究进展[J]. , 2010, 22(6): 480-483.
[7]	张娟;朱方艳;尹立红;浦跃朴. 苯和甲醛对BALB/c小鼠的联合遗传毒性[J]. , 2010, 22(4): 308-311.
[8]	彭国庆1;2;钟才高1;张琼2;关岚1;余剑英2;肖芳1. 甲醛对雌性大鼠卵巢储备功能的影响[J]. , 2010, 22(1): 32-0034.
[9]	吴成秋1;2;李纯颖2;李梓民2;张英彪2;陈立章1. 苯与甲醛对小鼠胚胎的联合毒性效应研究[J]. , 2009, 21(6): 455-459.
[10]	张桂芝1；刘东山2；刘长庭1. 甲醛对人支气管上皮细胞系染色体不稳定性的研究[J]. , 2006, 18(3): 165-170.
[11]	董杰影，楼哲丰，郑　重，金龙金. 用单细胞凝胶电泳技术检测甲醛对小鼠睾丸细胞的DNA损伤[J]. , 2004, 16(3): 148-150.
[12]	张遵真, 衡正昌. 甲醛和丝裂霉素C 的DNA 交联作用研究[J]. , 2001, 13(2): 74-076.