Salidroside-Mediated Neuroprotection is Associated with Induction of Early Growth Response Genes (Egrs) Across a Wide Therapeutic Window

详细信息    查看全文

• 作者：Wenfang Lai ; Zhenwei Zheng ; Xiaoqin Zhang ; Yicong Wei ; Kedan Chu…
• 关键词：Salidroside ; Brain ischemia ; Microarray analysis ; PC12 cells
• 刊名：Neurotoxicity Research
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：28
• 期：2
• 页码：108-121
• 全文大小：4,636 KB
• 参考文献：Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27:1616-623PubMed View Article
  Beschorner R, Schluesener HJ, Gozalan F, Meyermann R, Schwab JM (2002) Infiltrating CD14+ monocytes and expression of CD14 by activated parenchymal microglia/macrophages contribute to the pool of CD14+ cells in ischemic brain lesions. J Neuroimmunol 126:107-15PubMed View Article
  Bozon B, Davis S, Laroche S (2002) Regulated transcription of the immediate-early gene Zif268: mechanisms and gene dosage-dependent function in synaptic plasticity and memory formation. Hippocampus 12:570-77PubMed View Article
  Bozon B, Davis S, Laroche S (2003) A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 40:695-01PubMed View Article
  Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95:11715-1720PubMed Central PubMed View Article
  Chen SF, Tsai HJ, Hung TH, Chen CC, Lee CY, Wu CH, Wang PY, Liao NC (2012) Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury. PLoS One 7:e45763PubMed Central PubMed View Article
  DeSteno DA, Schmauss C (2008) Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task. Neuroscience 152:417-28PubMed Central PubMed View Article
  Fujimoto M, Takagi Y, Aoki T, Hayase M, Marumo T, Gomi M, Nishimura M, Kataoka H, Hashimoto N, Nozaki K (2008) Tissue inhibitor of metalloproteinases protect blood–brain barrier disruption in focal cerebral ischemia. J Cereb Blood Flow Metab 28:1674-685PubMed View Article
  Goldberg MA, Dunning SP, Bunn HF (1988) Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science 242:1412-415PubMed View Article
  Goldstein LB (2007) Acute ischemic stroke treatment in 2007. Circulation 116:1504-514PubMed View Article
  Guzowski JF, Lyford GL, Stevenson GD, Houston FP, McGaugh JL, Worley PF, Barnes CA (2000) Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J Neurosci 20:3993-001PubMed
  Hartwig K, Fackler V, Jaksch-Bogensperger H, Winter S, Furtner T, Couillard-Despres S, Meier D, Moessler H, Aigner L (2014) Cerebrolysin protects PC12 cells from CoCl2-induced hypoxia employing GSK3beta signaling. Int J Dev Neurosci 38:52-8PubMed View Article
  Hong G, Lockhart A, Davis B, Rahmoune H, Baker S, Ye L, Thompson P, Shou Y, O’Shaughnessy K, Ronco P, Brown J (2003) PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. FASEB J 17:1966-968PubMed
  Honkaniemi J, Sharp FR (1996) Global ischemia induces immediate-early genes encoding zinc finger transcription factors. J Cereb Blood Flow Metab 16:557-65PubMed View Article
  Hu J, Zhao TZ, Chu WH, Luo CX, Tang WH, Yi L, Feng H (2010) Protective effects of 20-hydroxyecdysone on CoCl2-induced cell injury in PC12 cells. J Cell Biochem 111:1512-521PubMed View Article
  Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1-3PubMed Central View Article
  Jiang BH, Zheng JZ, Leung SW, Roe R, Semenza GL (1997) Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tension. J Biol Chem 272:19253-9260PubMed View Article
  Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779-89PubMed Central PubMed View Article
  Kiyota Y, Pahlmark K, Memezawa H, Smith ML, Siesjo BK (1993) Free radicals and brain damage due to transient middle cerebral artery occlusion: the effect of dimethylthiourea. Exp Brain Res 95:388-96PubMed View Article
  Kotake-Nara E, Takizawa S, Quan J, Wang H, Saida K (2005) Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells through regulation of endothelin-2/vasoactive intestinal contractor. J Neurosci Res 81:563-71PubMed View Article
  Leung SB, Zhang H, Lau CW, Huang Y, Lin Z (2013) Salidroside improves homocysteine-induced endothelial dysfunction by reducing oxidative stress. Evid Based Complement Alternat Med 2013:679635PubMed Central PubMed
  Li W (2012) Volcano plots in analyzing differential expressions with mRNA microarrays. J Bioinform Comput Biol 10(6):1231003PubMed View Article
  Li L, Carter J, Gao X, Whitehead J, Tourtellotte WG (2005) The neuroplasticity-associated arc gene is a direct transcriptional target of e
• 作者单位：Wenfang Lai (1)
  Zhenwei Zheng (1)
  Xiaoqin Zhang (1)
  Yicong Wei (1)
  Kedan Chu (1)
  John Brown (1)
  Guizhu Hong (1)
  Lidian Chen (1)
  
  1. Centre of Biomedical Research & Development, Fujian University of Traditional Chinese Medicine, No. 1 Huatou Road, Minhou Shangjie, Fuzhou, China
  
• 刊物主题：Neurosciences; Neurology; Neurochemistry; Pharmacology/Toxicology; Neurobiology; Cell Biology;
• 出版者：Springer US
• ISSN：1476-3524

文摘

Salidroside exhibits anti-inflammatory, anti-oxidative, and anti-apoptotic properties. To identify whether salidroside might be a candidate for treating ischemic stroke, we investigated the effects of salidroside or vehicle, given daily for 6 days, after middle cerebral artery occlusion (MCAO) for 2?h and reperfusion for either 1 or 48?h in rats. Salidroside reduced cerebral infarct volume and significantly improved neurological scores whether started after 1 or 48?h of reperfusion. Microarray analysis showed that 20?% (133/678) of the genes down-regulated by ischemia and 1?h of reperfusion were up-regulated by salidroside, whereas 13?% (105/829) of the genes induced by ischemia–reperfusion were inhibited by salidroside, suggesting that salidroside can reverse effects of ischemia–reperfusion on gene expression. The main enriched functional categories induced by salidroside were genes related to synaptic plasticity, whereas salidroside inhibited genes related to inflammation. Induction of Egr1, Egr2, Egr4, and Arc by salidroside was confirmed by qRT-PCR and western blotting in ischemic brains treated after either 1 or 48?h of reperfusion. The potential protective role of Egr4 in salidroside-mediated neuroprotection was subsequently investigated in CoCl2-treated PC12 cells. Egr4 was dose-dependently induced by salidroside in PC12 cells, and depleting Egr4 with target-specific siRNA increased caspase-3 activity and Bax, but decreased Bcl-xl, which were reversed by salidroside. Finally, we confirmed that salidroside inhibited the Bax/Bcl-xl-related apoptosis after MCAO with reperfusion. In conclusion, salidroside is highly neuroprotective with a wide therapeutic time window after ischemia–reperfusion injury in the rat, and this partially involves induction of Egrs, leading to inhibition of Bax/Bcl-xl-related apoptosis.