Luteolin‑induced protection of H2O2‑induced apoptosis in PC12 cells and the associated pathway

Lin,Peng; Tian,Xing‑Han; Yi,Yong‑Shang; Jiang,Wen‑Shi; Zhou,Ying‑Jie; Cheng,Wen‑Jing

doi:10.3892/mmr.2015.4400

Luteolin‑induced protection of H2O2‑induced apoptosis in PC12 cells and the associated pathway

Authors:
- Peng Lin
- Xing‑Han Tian
- Yong‑Shang Yi
- Wen‑Shi Jiang
- Ying‑Jie Zhou
- Wen‑Jing Cheng
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Affiliations: Department of Intensive Care Unit, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong 264000, P.R. China, Department of Neurology, Seaport Hospital Shandong, Yantai, Shandong 264000, P.R. China, Department of Intensive Care Unit, People's Hospital of Yangshuo County, Yangshuo, Guangxi 541900, P.R. China, Department of Neurology, No. 1 People's Hospital of Jining, Jining, Shandong 272000, P.R. China
Published online on: September 30, 2015 https://doi.org/10.3892/mmr.2015.4400
Pages: 7699-7704

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Abstract

Increasing evidence has indicated that the generation of reactive oxygen species (ROS) contributes to H2O2‑induced nerve injury. This may result in oxidative stress that leads to cell damage or death. Dietary or pharmaceutical augmentation of the endogenous antioxidant defense capacity is a potential means by which to prevent ROS‑induced damage. The aim of the current study was to investigate the effect of luteolin on H2O2‑induced cell apoptosis in cultured rat pheochromocytoma cells (PC12 cells) and to investigate the role of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (Akt) pathway on H2O2‑induced apoptosis. The results demonstrated that luteolin was able to inhibit the reduction in cell viability induced by H2O2. In addition, luteolin reduced ROS generation and lactate dehydrogenase release in H2O2‑treated PC12 cells. The levels of superoxide dismutase and glutathione peroxidase activity were increased following treatment with luteolin, however malondialdehyde levels were observed to be reduced. Additionally, luteolin increased the Bcl‑2/Bax ratio and enhanced Akt phosphorylation. However, these alterations were attenuated by pretreatment with an inhibitor of the PI3K/Akt pathway. In conclusion, luteolin inhibited H2O2‑induced apoptosis via reducing ROS levels and activating the PI3K/Akt pathway.

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1	Fahn S and Cohen G: The oxidant stress hypothesis in Parkinson's disease: Evidence supporting it. Ann Neurol. 32:804–812. 1992. View Article : Google Scholar : PubMed/NCBI
2	Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF and Kowall N: Oxidative damage in Alzheimer's. Nature. 382:120–121. 1996. View Article : Google Scholar : PubMed/NCBI
3	Halliwell B: Oxidative stress and neurodegeneration: Where are we now? J Neurochem. 97:1634–1658. 2006. View Article : Google Scholar : PubMed/NCBI
4	Li MH, Jang JH, Sun B and Surh YJ: Protective effects of oligomers of grape seed polyphenols against beta-amyloid-induced oxidative cell death. Ann N Y Acad Sci. 1030:317–329. 2004. View Article : Google Scholar
5	Fukui K, Takatsu H, Shinkai T, Suzuki S, Abe K and Urano S: Appearance of amyloid beta-like substances and delayed-type apoptosis in rat hippocampus CA1 region through aging and oxidative stress. J Alzheimers Dis. 8:299–309. 2005.PubMed/NCBI
6	Kadowaki H, Nishitoh H, Urano F, Sadamitsu C, Matsuzawa A, Takeda K, Masutani H, Yodoi J, Urano Y, Nagano T and Ichijo H: Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death Differ. 12:19–24. 2005. View Article : Google Scholar
7	Heo SR, Han AM and Kwon YK: p62 protects SH-SY5Y neuroblastoma cells against H2O2-induced injury through the PDK1/Akt pathway. Neurosci Lett. 23;450(1): 45–50. 2009. View Article : Google Scholar
8	Satoh T, Sakai N, Enokido Y, Uchiyama Y and Hatanaka H: Free radical-independent protection by nerve growth factor and Bcl-2 of PC12 cells from hydrogen peroxide-triggered apoptosis. J Biochem. 120:540–546. 1996. View Article : Google Scholar : PubMed/NCBI
9	Yu BP and Yang R: Critical evaluation of the free radical theory of aging. A proposal for the oxidative stress hypothesis. Ann N Y Acad Sci. 786(1 Near-Earth Ob): 1–11. 1996. View Article : Google Scholar : PubMed/NCBI
10	Floyd RA: Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med. 222:236–245. 1999. View Article : Google Scholar : PubMed/NCBI
11	Sultana R, Newman S, Mohmmad-Abdul H, Keller JN and Butterfield DA: Protective effect of the xanthate, D609, on Alzheimer's amyloid betapeptide (1–42)-induced oxidative stress in primary neuronal cells. Free Radic Res. 38:449–458. 2004. View Article : Google Scholar : PubMed/NCBI
12	Koh SH, Kwon H, Park KH, Ko JK, Kim JH, Hwang MS, Yum YN, Kim OH, Kim J, Kim HT, et al: Protective effect of diallyl disulfide on oxidative stress-injured neuronally differentiated PC12 cells. Brain Res Mol Brain Res. 133:176–186. 2005. View Article : Google Scholar : PubMed/NCBI
13	Choi SJ, Kim MJ, Heo HJ, Hong B, Cho HY, Kim YJ, Kim HK, Lim ST, Jun WJ, Kim EK and Shin DH: Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide-induced neuronal cell deficit. Mol Cells. 24:113–118. 2007.PubMed/NCBI
14	Zhang HY, Liu YH, Wang HQ, Xu JH and Hu HT: Puerarin protects PC12 cells against beta-amyloid-induced cell injury. Cell Biol Int. 32:1230–1237. 2008. View Article : Google Scholar : PubMed/NCBI
15	Soubra L, Sarkis D, Hilan C and Verger P: Dietary exposure of children and teenagers to benzoates, sulphites, butylhydroxyanisol (BHA) and butylhydroxytoluen (BHT) in Beirut (Lebanon). Regul Toxicol Pharmacol. 47:68–77. 2007. View Article : Google Scholar
16	Pandurangan AK, Dharmalingam P, Ananda Sadagopan SK and Ganapasam S: Effect of luteolin on the levels of glycoproteins during azoxymethane-induced colon carcinogenesis in mice. Asian Pac J Cancer Prev. 13:1569–1573. 2012. View Article : Google Scholar : PubMed/NCBI
17	Jung HA, Jin SE, Min BS, Kim BW and Choi JS: Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside. Food Chem Toxicol. 50:2171–2179. 2012. View Article : Google Scholar : PubMed/NCBI
18	Manju V and Nalini N: Protective role of luteolin in 1,2-dimeth-ylhydrazine induced experimental colon carcinogenesis. Cell Biochem Funct. 25:189–194. 2007. View Article : Google Scholar
19	Sun GB, Sun X, Wang M, Ye JX, Si JY, Xu HB, Meng XB, Qin M, Sun J, Wang HW and Sun XB: Oxidative stress suppression by luteolin-induced heme oxygenase-1 expression. Toxicol Appl Pharmacol. 265:229–240. 2012. View Article : Google Scholar : PubMed/NCBI
20	Casagrande F and Darbon JM: Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: Regulation of cyclin-dependent kinases CDK2 and CDK1. Biochem Pharmacol. 61:1205–1215. 2001. View Article : Google Scholar : PubMed/NCBI
21	Matsui T, Kobayshi M, Hayashida S and Matsumoto K: Luteolin, a flavone, does not suppress post prandial blood glucose absorption through the inhalation of alpha-glucosidase action. Biosci, Biotechnol and Biochem. 66:689–692. 2002. View Article : Google Scholar
22	Ji BS and Gao Y: Protective effect of trihexyphenidyl on hydrogen peroxide-induced oxidative damage in PC12 cells. Neurosci Lett. 437:50–54. 2008. View Article : Google Scholar : PubMed/NCBI
23	Lee YM, Park SH, Shin DI, Hwang JY, Park B, Park YJ, Lee TH, Chae HZ, Jin BK, Oh TH and Oh YJ: Oxidative modification of peroxiredoxin is associated with drug-induced apoptotic signaling in experimental models of Parkinson disease. J Biol Chem. 283:9986–9998. 2008. View Article : Google Scholar : PubMed/NCBI
24	Markesbery WR: Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 23:134–147. 1997. View Article : Google Scholar : PubMed/NCBI
25	Jenner P: Oxidative stress in Parkinson's disease. Ann Neurol. 53(Suppl 3): S26–S36; discussion S36–S38. 2003. View Article : Google Scholar : PubMed/NCBI
26	Emerit J, Edeas M and Bricaire F: Neurodegenerative diseases and oxidative stress. Biomed Pharmacother. 58:39–46. 2004. View Article : Google Scholar : PubMed/NCBI
27	Gozal E, Sachleben LR Jr, Rane MJ, Vega C and Gozal D: Mild sustained and intermittent hypoxia induce apoptosis in PC-12 cells via different mechanisms. Am J Physiol Cell Physiol. 288:C535–C542. 2005. View Article : Google Scholar
28	Hirose M, Takatori M, Kuroda Y, Abe M, Murata E, Isada T, Ueda K, Shigemi K, Shibazaki M, Shimizu F, et al: Effect of synthetic cell-penetrating peptides on TrkA activity in PC12 cells. J Pharmacol Sci. 106:107–113. 2008. View Article : Google Scholar : PubMed/NCBI
29	Wang J, Zhang QB, Zhang ZS, Zhang JJ and Li PC: Synthesized phosphorylated and aminated derivatives of fucoidan and their potential antioxidant activity in vitro. Int J Biol Macromol. 44:170–174. 2009. View Article : Google Scholar
30	Erten SF, Kocak A, Ozdemir I, Aydemir S, Colak A and Reeder BS: Protective effect of melatonin on experimental spinal cord ischemia. Spinal Cord. 41:533–538. 2003. View Article : Google Scholar : PubMed/NCBI
31	Qian H and Liu D: The time course of malondialdehyde production following impact injury to rat spinal cord as measured by microdialysis and high pressure liquid chromatography. Neurochem Res. 22:1231–1236. 1997. View Article : Google Scholar : PubMed/NCBI
32	Misao J, Hayakawa Y, Ohno M, Kato S, Fujiwara T and Fujiwara H: Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation. 94:1506–1512. 1996. View Article : Google Scholar : PubMed/NCBI
33	Wang R, Zhang HY and Tang XC: Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1–40) in rat. Eur J Pharmacol. 421:149–156. 2001. View Article : Google Scholar : PubMed/NCBI
34	Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y and Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231–241. 1997. View Article : Google Scholar : PubMed/NCBI
35	Martin D, Salinas M, Fujita N, Tsuruo T and Cuadrado A: Ceramide and reactive oxygen species generated by H₂O₂ induce caspase-3-independent degradation of Akt/protein kinase B. J Biol Chem. 277:42943–42952. 2002. View Article : Google Scholar : PubMed/NCBI
36	Wang X, McCullough KD, Franke TF and Holbrook NJ: Epidermal growth factor receptor-dependent Akt activation by oxidative stress enhances cell survival. J Biol Chem. 275:14624–14631. 2000. View Article : Google Scholar : PubMed/NCBI
37	Ma R, Xiong N, Huang C, Tang Q, Hu B, Xiang J and Li G: Erythropoietin protects PC12 cells from beta-amyloid(25–35)-induced apoptosis via PI3K/Akt signaling pathway. Neuropharmacology. 56:1027–1034. 2009. View Article : Google Scholar : PubMed/NCBI