Cytotoxicity of oxidized low-density lipoprotein on PC12 cells

Abstract

Abstract: AIM: To investigate the cytotoxicity of oxidized low-density lipoprotein (oxLDL) on PC12 cells.METHODS: PC12 cells were applied to be a neuron model and exposed to oxLDL.Cell injury was evaluated by cell viability (MTT assay), cell lysis (LDH assay), DNA fragmentation (TUNEL assay) and Caspase-3 activity (Caspase assay).RESULTS: Most of PC12 cells treated with oxLDL showed cell lysis changes and a few cells showed apoptotic changes, observed with electromicroscopically .The cell viability decreased with the concentration of oxLDL increasing.As the concentration of oxLDL increased, LDH release, DNA fragmentation and Caspase-3 activity also increased.However, there was no significant alteration in untreated control cultures and LDL control.CONCLUSION: oxLDL, but not native LDL, resultes in a dose- and time-dependent neuron death including cell lysis and apoptosis in which Caspases-3 participates.

Key words: oxidized low-density lipoprotein, PC12 cells, cytotoxicity

CLC Number:

R963

CAO Li, YIN Hong-Cao, ZHOU Li, WANG Yong-Jun. Cytotoxicity of oxidized low-density lipoprotein on PC12 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(2): 166-170.

References

1 Dehouc B, Fenart L, Dehouc MP, Pierce A, Torpier G, Cecchelli R.A new function for the receptor:Transcytosis of LDL across the blood-brain barrier[J]. J Cell Biol, 1997 ;138(4):877-99
2 Newcombe J, Li H, Cuzner ML.Low-density lipoprotein uptake by macrophages in MS plaques:Implications for pathogenesis[J]. Neuropathol Appl Neurobiol, 1994;20(2):152-62
3 Leppala J, Kallio M, Nikula T, Nikkinen P, Liewendahl K, Jaaskelainen J, et al. Accumulation of 99mTc low-density lipoprotein in human malignant glioma[J]. Br J Cancer, 1995 ;71(2):383-7
4 Mato M, Oolkawara S, Sakamoto A, Aikawa E, Ogawa T, Mitsuhashi U, et al. Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex[J]. Proc Natl Acad Sci, 1996 ;USA93(8):3269-74
5 Lucarelli M, Gennarelli M, Cardelli P, Novelli G, Scarpa S, Dallapiccola B, et al. Expression of receptors for native and chemically modified LDL in brain microvessels[J]. FEBS Lett,1997;40(1):53-8
6 Christie RH, Freeman M, Hyman BT.Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in the microglia associated with senile plaques in Alzheimer' s disease[J]. Am J Pathol, 1996 ;148(2):399-403
7 Papassotiropoulos A, Ludwig M, Naib-Majani W, Rao G.S.Induction of apoptosis and secondary necrosis in rat dorsal root ganglion cell cultures by oxidized low-density lipoprotein[J]. Neurosci Lett, 1996 ;209(1):33-6
8 Sugawa M, Ikeda S, Kushima Y, Takashima Y, Cynshi O.Oxidized low-density lipoprotein caused CNS neuron cell death[J]. Brain Res, 1997 ;761(1):165-72
9 Draczynska-lusiak B, Doung A, Sun AY.Oxidized lipoproteins may play a role in neuronal cell death in Alzheimer disease[J]. Mol Chem Neuropalthol, 1998;33(2):139-48
10 Keller JN, Hanni KB, Pedersen WA, Cashman NR, Mattson MP, Gabbita SP, et al. Opposing actions of native and oxidized lipoprotein on motor neuron-like cells[J]. Exp Neurol, 1999;57(1):202-10
11 Keller JN, Hanni KB, Markesbery WR.Oxidized low-density lipoprotein induces neuronal death:implication for calcium, reactive oxygen species, and caspases[J]. J Neurochem, 1999;72(6):2601-9
12 Schroeter H, Williams RJ, Matin R, Iversen L, Rice-Evans CA.Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein[J]. Free RadicBiol Med, 2000;29(12):1222-3
13 Steinberg D, Low-density lipoprotein oxidation and its pathobiological significance[J]. J Biol Chem, 1997;272(34):20963-6

[1]	LIN Naping, WU Yutang, HUANG Defen, XU Chaoxiang. Effects of miR-195-5p on ox-LDL-induced vascular endothelial cell injury through regulating FBXW7 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(2): 163-170.
[2]	HE Yin, BAO Yuting, YAO Ying, XUAN Ling, YANG Yuanxiao. Protective effects of β-asarone on PC12 cells injury induced by Aβ_1-42 activated ACM [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 608-613.
[3]	XIAO Shi-geng, DONG Wen-bin, CHENG Min, YE Xiao-di, ZHENG Gao-li. Autophagy activation contributes to the protection of minocycline against oxygen-glucose deprivation and reperfusion in PC12 cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(2): 145-150.
[4]	CHEN Xue-mei, LIU Jun, SONG Jin-ping, WANG Tao, SHANG Jing. Preliminary toxicological study of colchicine in rat renal cells NRK [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(5): 496-500.
[5]	LI Ai-si, HUANG Yong-ping, LIU Jian-wen, LAN Min-bo, GAO Feng, XU Hao-liang, CHEN Ming-cang, XU Yi-chun. Oxidative lesions induced by medical SiO₂ nanoparticles on normal human lung cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(10): 1115-1120.
[6]	LIU Ping, HONG Hao. Scutellarin attenuates hydrogen peroxide-induced apoptosis in PC12 cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(3): 283-287.
[7]	LIU Mi-feng, PENG Shuang-qing, SHENG Zhi-guo, XIE Yue-hua, DONG Yan-sheng, YANG Haiying, HAN Gang, YAN Chang-hui. Research on correlations between cytotoxicity and acute toxicity of seven compounds [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(1): 42-45.
[8]	GUO Ming-chuan, CAO Yan, LIU Jian-wen. Protective effects of picroside Ⅱon glutamate injury of PC12 cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(4): 440-443.
[9]	WANG Qiang, XU Li-xian, ZHANG Hui, ZHU Xiao-ling, XIONG Li-ze. Effect of propofol on cytotoxicity and endogenous thioredoxin system induced by bupivacaine in pheochromocytoma PC12 cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(3): 282-286.
[10]	WANG Yi-mei, PENG Shuang-qing, ZHONG Bo-hua, LIU Ke-liang. Cytotoxicity evaluation of a novel anticholinergicdrug penehyclidine hydrochloride and its optical isomers [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(12): 1389-1389.
[11]	SONG Jue, LU Tong, XIE Lin, WANG Guang-ji, LIU Xiao-dong. Studies on correlation between pharmacodynemics and pharmacokenitics characteristics of baicalin using serum pharamoclogical test in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(12): 1350-1354.
[12]	DAI Xiao-ming , SUN Rong , WU Dong-dong , WU Yu-lin. Protective effects of Hypericum perforatum on ischemic injury in PC12 cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(1): 51-54.
[13]	ZHAN Xiao-Yun, REN Yu-Hong, ZHANG Qiang, LU Yan-Hua, WEI Dong-Zhi, LIU Jian-Wen. A novel antisense oligodeoxynucleotide-doxorubicin conjugate against the multidrug resistance gene mdr1:inhibition to KB-A-1 cell and P-glycoprotein expression [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(4): 403-410.
[14]	YANG Zhi-Yong, LIU Guo-Qing, HUANG Wen-Long¹. Effects of novel tetrahydroisoquinoline derivative-H108 on activity of P-glycoprote in virto and injury of PC12 cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 275-280.
[15]	HUO Guan-Hua, LU Yao-Feng, ZHANG Jin-Feng, GAO Hong -Qiu. Cytotoxicity induced by a combination ofγ-radiation with menadione sodium bisulfates on HeLa cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2003, 8(5): 530-533.