Resveratrol pretreatment attenuates injury and promotes proliferation of neural stem cells following oxygen-glucose deprivation/reoxygenation by upregulating the expression of Nrf2, HO-1 and NQO1 in vitro

Shen,Changbo; Cheng,Wei; Yu,Pingping; Wang,Li; Zhou,Lulin; Zeng,Li; Yang,Qin

doi:10.3892/mmr.2016.5670

Resveratrol pretreatment attenuates injury and promotes proliferation of neural stem cells following oxygen-glucose deprivation/reoxygenation by upregulating the expression of Nrf2, HO-1 and NQO1 in vitro

Authors:
- Changbo Shen
- Wei Cheng
- Pingping Yu
- Li Wang
- Lulin Zhou
- Li Zeng
- Qin Yang
View Affiliations

Affiliations: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: August 24, 2016 https://doi.org/10.3892/mmr.2016.5670
Pages: 3646-3654
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

There is considerable interest in the use of drugs and other methods for protecting implanted neural stem cells (NSCs) from the adverse environment of injured tissue for successful cell therapy. Resveratrol can modify cardiac stem cells to enhance their survival and differentiation, however, its effect and the mechanism underlying its neuroprotective effect on NSCs following stroke remain to be fully elucidated. Nuclear factor erythroid 2‑related factor 2 (Nrf‑2) signaling is important in antioxidative stress, and the role of Nrf‑2 signaling in the enhanced neuroprotection of NSCs by resveratrol following stroke also remains to be elucidated. In the present study, NSCs were pretreated with resveratrol prior to oxygen‑glucose deprivation/reoxygenation (OGD/R) in vitro. The survival, apoptosis and proliferation of the NSCs were assessed using an MTT assay, Hoechst 33258 staining of nuclei and flow cytometry, respectively. In addition, the activity of superoxide dismutase (SOD), level of malondiadehyde (MDA) and content of glutathione (GSH) were determined. The protein expressions levels of Nrf‑2, NAD(P)H:quinone oxidoreductase 1 (NQO‑1), and heme oxygenase 1 (HO‑1) were detected using western blot analysis. It was found that resveratrol markedly enhanced NSC survival and proliferation, decreased apoptosis and the levels of MDA, and increased the activity of SOD and content of GSH in a concentration‑dependent manner following OGD/R injury in vitro. In addition, the protein expression levels of Nrf2, HO‑1 and NQO1 were significantly upregulated. These findings suggested that resveratrol attenuated injury and promoted proliferation of the NSCs, at least in part, by upregulating the expression of Nrf2, HO‑1 and NQO1 following OGD/R injury in vitro.

View Figures

View References

1	Keuters MH, Aswendt M, Tennstaedt A, Wiedermann D, Pikhovych A, Rotthues S, Fink GR, Schroeter M, Hoehn M and Rueger MA: Transcranial direct current stimulation promotes the mobility of engrafted NSCs in the rat brain. NMR Biomed. 28:231–239. 2015. View Article : Google Scholar
2	Lu P, Graham L, Wang Y, Wu D and Tuszynski M: Promotion of survival and differentiation of neural stem cells with fibrin and growth factor cocktails after severe spinal cord injury. J Vis Exp. e506412014.PubMed/NCBI
3	Sarnowska A, Jablonska A, Jurga M, Dainiak M, Strojek L, Drela K, Wright K, Tripathi A, Kumar A, Jungvid H, et al: Encapsulation of mesenchymal stem cells by bioscaffolds protects cell survival and attenuates neuroinflammatory reaction in injured brain tissue after transplantation. Cell Transplant. 22(Suppl 1): S67–S82. 2013. View Article : Google Scholar : PubMed/NCBI
4	Tang S, Liao X, Shi B, Qu Y, Huang Z, Lin Q, Guo X and Pei F: The effects of controlled release of neurotrophin-3 from PCLA scaffolds on the survival and neuronal differentiation of transplanted neural stem cells in a rat spinal cord injury model. PLoS One. 9:e1075172014. View Article : Google Scholar : PubMed/NCBI
5	Liang Y, Walczak P and Bulte JW: The survival of engrafted neural stem cells within hyaluronic acid hydrogels. Biomaterials. 34:5521–5529. 2013. View Article : Google Scholar : PubMed/NCBI
6	Walle T: Bioavailability of resveratrol. Ann N Y Acad Sci. 1215:9–15. 2011. View Article : Google Scholar : PubMed/NCBI
7	Baur JA and Sinclair DA: Therapeutic potential of resveratrol: The in vivo evidence. Nat Rev Drug Discov. 5:493–506. 2006. View Article : Google Scholar : PubMed/NCBI
8	Lin HY, Tang HY, Davis FB and Davis PJ: Resveratrol and apoptosis. Ann N Y Acad Sci. 1215:79–88. 2011. View Article : Google Scholar : PubMed/NCBI
9	Sinha K, Chaudhary G and Gupta YK: Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci. 71:655–665. 2002. View Article : Google Scholar : PubMed/NCBI
10	Jin F, Wu Q, Lu YF, Gong QH and Shi JS: Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson's disease in rats. Eur J Pharmacol. 600:78–82. 2008. View Article : Google Scholar : PubMed/NCBI
11	Li F, Gong Q, Dong H and Shi J: Resveratrol, a neuroprotective supplement for Alzheimer's disease. Curr Pharm Des. 18:27–33. 2012. View Article : Google Scholar : PubMed/NCBI
12	Li Z, Pang L, Fang F, Zhang G, Zhang J, Xie M and Wang L: Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2. Brain Res. 1450:116–124. 2012. View Article : Google Scholar : PubMed/NCBI
13	Madhyastha S, Sekhar S and Rao G: Resveratrol improves postnatal hippocampal neurogenesis and brain derived neurotrophic factor in prenatally stressed rats. Int J Dev Neurosci. 31:580–585. 2013. View Article : Google Scholar : PubMed/NCBI
14	Moriya J, Chen R, Yamakawa J, Sasaki K, Ishigaki Y and Takahashi T: Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells. Biol Pharm Bull. 34:354–359. 2011. View Article : Google Scholar : PubMed/NCBI
15	Ren JW, Fan C, Chen N, Huang J and Yang Q: Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating expression of transcription factor Nrf2 and HO-1 in rats. Neurochem Res. 36:2352–2362. 2011. View Article : Google Scholar : PubMed/NCBI
16	Gorbunov N, Petrovski G, Gurusamy N, Ray D, Kim doH and Das DK: Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells. J Cell Mol Med. 16:174–184. 2012. View Article : Google Scholar
17	Mohagheghi F, Khalaj L, Ahmadiani A and Rahmani B: Gemfibrozil pretreatment affecting antioxidant defense system and inflammatory, but not Nrf-2 signaling pathways resulted in female neuroprotection and male neurotoxicity in the rat models of global cerebral ischemia-reperfusion. Neurotox Res. 23:225–237. 2013. View Article : Google Scholar
18	Zhang DD: Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug metab Rev. 38:769–789. 2006. View Article : Google Scholar : PubMed/NCBI
19	Ping Z, Liu W, Kang Z, Cai J, Wang Q, Cheng N, Wang S, Wang S, Zhang JH and Sun X: Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme. Brain Res. 1343:178–185. 2010. View Article : Google Scholar : PubMed/NCBI
20	Reynolds BA, Tetzlaff W and Weiss S: A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci. 12:4565–4574. 1992.PubMed/NCBI
21	Andersen RK, Johansen M, Blaabjerg M, Zimmer J and Meyer M: Neural tissue-spheres: A microexplant culture method for propagation of precursor cells from the rat forebrain subventricular zone. J Neurosci Methods. 165:55–63. 2007. View Article : Google Scholar : PubMed/NCBI
22	Babu H, Claasen JH, Kannan S, Rünker AE, Palmer T and Kempermann G: A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus. Front Neurosci. 5:892011. View Article : Google Scholar : PubMed/NCBI
23	Chen T, Liu W, Chao X, Qu Y, Zhang L, Luo P, Xie K, Huo J and Fei Z: Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: Involvement of mitogen-activated protein kinase pathway. Neuroscience. 183:203–211. 2011. View Article : Google Scholar : PubMed/NCBI
24	Wu X, Zhao J, Yu S, Chen Y, Wu J and Zhao Y: Sulforaphane protects primary cultures of cortical neurons against injury induced by oxygen-glucose deprivation/reoxygenation via anti-apoptosis. Neurosci Bull. 28:509–516. 2012. View Article : Google Scholar : PubMed/NCBI
25	Harada N, Zhao J, Kurihara H, Nakagata N and Okajima K: Resveratrol improves cognitive function in mice by increasing production of insulin-like growth factor-I in the hippocampus. J Nutr Biochem. 22:1150–1159. 2011. View Article : Google Scholar : PubMed/NCBI
26	Park HR, Kong KH, Yu BP, Mattson MP and Lee J: Resveratrol inhibits the proliferation of neural progenitor cells and hippocampal neurogenesis. J Biol Chem. 287:42588–42600. 2012. View Article : Google Scholar : PubMed/NCBI
27	Leong CW, Wong CH, Lao SC, Leong EC, Lao IF, Law PT, Fung KP, Tsang KS, Waye MM, Tsui SK, et al: Effect of resveratrol on proliferation and differentiation of embryonic cardiomyoblasts. Biochem Biophys Res Commun. 360:173–180. 2007. View Article : Google Scholar : PubMed/NCBI
28	Slemmer JE, Shacka JJ, Sweeney MI and Weber JT: Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem. 15:404–414. 2008. View Article : Google Scholar : PubMed/NCBI
29	Nassar NN, Abdelsalam RM, Abdel-Rahman AA and Abdallah DM: Possible involvement of oxidative stress and inflammatory mediators in the protective effects of the early preconditioning window against transient global ischemia in rats. Neurochem Res. 37:614–621. 2012. View Article : Google Scholar
30	Oh YI, Kim JH and Kang CW: Protective effect of short-term treatment with parathyroid hormone 1-34 on oxidative stress is involved in insulin-like growth factor-I and nuclear factor erythroid 2-related factor 2 in rat bone marrow derived mesenchymal stem cells. Regul Pept. 189:1–10. 2014. View Article : Google Scholar : PubMed/NCBI
31	De la Lastra CA and Villegas I: Resveratrol as an antioxidant and pro-oxidant agent: Mechanisms and clinical implications. Biochem Soc Trans. 35:1156–1160. 2007. View Article : Google Scholar : PubMed/NCBI
32	Konyalioglu S, Armagan G, Yalcin A, Atalayin C and Dagci T: Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells. Neural Regen Res. 8:485–495. 2013.PubMed/NCBI
33	Maher J and Yamamoto M: The rise of antioxidant signaling-the evolution and hormetic actions of Nrf2. Toxicol Appl Pharmacol. 244:4–15. 2010. View Article : Google Scholar : PubMed/NCBI
34	Quincozes-Santos A, Bobermin LD, Latini A, Wajner M, Souza DO, Gonçalves CA and Gottfried C: Resveratrol protects C6 astrocyte cell line against hydrogen peroxide-induced oxidative stress through heme oxygenase 1. PloS One. 8:e643722013. View Article : Google Scholar : PubMed/NCBI
35	Yang C, Zhang X, Fan H and Liu Y: Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res. 1282:133–141. 2009. View Article : Google Scholar : PubMed/NCBI
36	Sakata Y, Zhuang H, Kwansa H, Koehler RC and Doré S: Resveratrol protects against experimental stroke: Putative neuroprotective role of heme oxygenase 1. Exp Neurol. 224:325–329. 2010. View Article : Google Scholar : PubMed/NCBI
37	Lin TK, Chen SD, Chuang YC, Lin HY, Huang CR, Chuang JH, Wang PW, Huang ST, Tiao MM, Chen JB and Liou CW: Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy. Int J Mol Sci. 15:1625–1646. 2014. View Article : Google Scholar : PubMed/NCBI
38	Ghanim H, Sia CL, Korzeniewski K, Lohano T, Abuaysheh S, Marumganti A, Chaudhuri A and Dandona P: A resveratrol and polyphenol preparation suppresses oxidative and inflammatory stress response to a high-fat, high-carbohydrate meal. J Clin Endocrinol Metab. 96:1409–1414. 2011. View Article : Google Scholar : PubMed/NCBI
39	Gurusamy N, Ray D, Lekli I and Das DK: Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium. J Cell Mol Med. 14:2235–2239. 2010. View Article : Google Scholar : PubMed/NCBI