nach oben

Neurotoxicity Research

Erschienen in:

01.08.2015 | Original Article

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

verfasst von: Wenfang Lai, Zhenwei Zheng, Xiaoqin Zhang, Yicong Wei, Kedan Chu, John Brown, Guizhu Hong, Lidian Chen

Erschienen in: Neurotoxicity Research | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

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.

Nur mit Berechtigung zugänglich

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 27:1616–1623PubMedCrossRef

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 126:107–115PubMedCrossRef

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 12:570–577PubMedCrossRef

Bozon B, Davis S, Laroche S (2003) A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 40:695–701PubMedCrossRef

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 95:11715–11720PubMedCentralPubMedCrossRef

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:e45763PubMedCentralPubMedCrossRef

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 152:417–428PubMedCentralPubMedCrossRef

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 28:1674–1685PubMedCrossRef

Goldberg MA, Dunning SP, Bunn HF (1988) Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science 242:1412–1415PubMedCrossRef

Goldstein LB (2007) Acute ischemic stroke treatment in 2007. Circulation 116:1504–1514PubMedCrossRef

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 20:3993–4001PubMed

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 38:52–58PubMedCrossRef

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 17:1966–1968PubMed

Honkaniemi J, Sharp FR (1996) Global ischemia induces immediate-early genes encoding zinc finger transcription factors. J Cereb Blood Flow Metab 16:557–565PubMedCrossRef

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 111:1512–1521PubMedCrossRef

Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13PubMedCentralCrossRef

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 272:19253–19260PubMedCrossRef

Jin R, Yang G, Li G (2010) Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 87:779–789PubMedCentralPubMedCrossRef

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 95:388–396PubMedCrossRef

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 81:563–571PubMedCrossRef

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 2013:679635PubMedCentralPubMed

Li W (2012) Volcano plots in analyzing differential expressions with mRNA microarrays. J Bioinform Comput Biol 10(6):1231003PubMedCrossRef

Li L, Carter J, Gao X, Whitehead J, Tourtellotte WG (2005) The neuroplasticity-associated arc gene is a direct transcriptional target of early growth response (Egr) transcription factors. Mol Cell Biol 25:10286–10300PubMedCentralPubMedCrossRef

Li X, Sipple J, Pang Q, Du W (2012) Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance. Blood 119:4162–4173PubMedCentralPubMedCrossRef

Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91PubMedCrossRef

Mengozzi M, Cervellini I, Villa P, Erbayraktar Z, Gokmen N, Yilmaz O, Erbayraktar S, Manohasandra M, Van Hummelen P, Vandenabeele P, Chernajovsky Y, Annenkov A, Ghezzi P (2012) Erythropoietin-induced changes in brain gene expression reveal induction of synaptic plasticity genes in experimental stroke. Proc Natl Acad Sci USA 109:9617–9622PubMedCentralPubMedCrossRef

Muresanu DF, Buzoianu A, Florian SI, von Wild T (2012) Towards a roadmap in brain protection and recovery. J Cell Mol Med 16:2861–2871PubMedCentralPubMedCrossRef

Nakayama H, Ginsberg MD, Dietrich WD (1988) (S)-emopamil a novel calcium channel blocker and serotonin S2 antagonist, markedly reduces infarct size following middle cerebral artery occlusion in the rat. Neurology 38:1667–1673PubMedCrossRef

Ohta H, Terao Y, Shintani Y, Kiyota Y (2007) Therapeutic time window of post-ischemic mild hypothermia and the gene expression associated with the neuroprotection in rat focal cerebral ischemia. Neurosci Res 57:424–433PubMedCrossRef

Piret JP, Mottet D, Raes M, Michiels C (2002) CoCl₂, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2. Ann NY Acad Sci 973:443–447PubMedCrossRef

Qu ZQ, Zhou Y, Zeng YS, Lin YK, Li Y, Zhong ZQ, Chan WY (2012) Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat. PLoS One 7:e29641PubMedCentralPubMedCrossRef

Shepherd JD, Bear MF (2011) New views of Arc, a master regulator of synaptic plasticity. Nat Neurosci 14:279–284PubMedCrossRef

Shi TY, Feng SF, Xing JH, Wu YM, Li XQ, Zhang N, Tian Z, Liu SB, Zhao MG (2012) Neuroprotective effects of salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and H₂O₂-induced neurotoxicity in vitro. Neurotox Res 21:358–367PubMedCrossRef

Smith WS (2004) Pathophysiology of focal cerebral ischemia: a therapeutic perspective. J Vasc Interv Radiol 15:S3–S12PubMedCrossRef

Spasov AA, Wikman GK, Mandrikov VB, Mironova IA, Neumoin VV (2000) A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine 7:85–89PubMedCrossRef

Traystman RJ, Kirsch JR, Koehler RC (1991) Oxygen radical mechanisms of brain injury following ischemia and reperfusion. J Appl Physiol 71:1185–1195PubMed

Wang G (2000) Mitochondrial DNA damage and a hypoxic response are induced by CoCl₂ in rat neuronal PC12 cells. Nucleic Acids Res 28:2135–2140PubMedCentralPubMedCrossRef

Wang H, Zhan Y, Xu L, Feuerstein GZ, Wang X (2001) Use of suppression subtractive hybridization for differential gene expression in stroke: discovery of CD44 gene expression and localization in permanent focal stroke in rats. Stroke 32:1020–1027PubMedCrossRef

Wang X, Xu L, Wang H, Zhan Y, Pure E, Feuerstein GZ (2002) CD44 deficiency in mice protects brain from cerebral ischemia injury. J Neurochem 83:1172–1179PubMedCrossRef

Wang S, Hu C, Jiang D, Peng J, Zhou Z, Yuan Q, Nie S, Jiang J, Li Y, Huang K (2009) All-trans retinoic acid inhibits cobalt chloride-induced apoptosis in PC12 cells: role of the dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine pathway. J Neurosci Res 87:1938–1946PubMedCrossRef

Williams J, Dragunow M, Lawlor P, Mason S, Abraham WC, Leah J, Bravo R, Demmer J, Tate W (1995) Krox20 may play a key role in the stabilization of long-term potentiation. Brain Res Mol Brain Res 28:87–93PubMedCrossRef

Xie B, Wang C, Zheng Z, Song B, Ma C, Thiel G, Li M (2011) Egr-1 transactivates Bim gene expression to promote neuronal apoptosis. J Neurosci 31:5032–5044PubMedCrossRef

Xu MC, Shi HM, Gao XF, Wang H (2013) Salidroside attenuates myocardial ischemia-reperfusion injury via PI3K/Akt signaling pathway. J Asian Nat Prod Res 15:244–252PubMedCrossRef

Yu S, Liu M, Gu X, Ding F (2008) Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation. Cell Mol Neurobiol 28:1067–1078PubMedCrossRef

Zhang L, Yu H, Sun Y, Lin X, Chen B, Tan C, Cao G, Wang Z (2007) Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells. Eur J Pharmacol 564:18–25PubMedCrossRef

Zhou M, Wang CM, Yang WL, Wang P (2013) Microglial CD14 activated by iNOS contributes to neuroinflammation in cerebral ischemia. Brain Res 1506:105–114PubMedCentralPubMedCrossRef

Zou W, Yan M, Xu W, Huo H, Sun L, Zheng Z, Liu X (2001) Cobalt chloride induces PC12 cells apoptosis through reactive oxygen species and accompanied by AP-1 activation. J Neurosci Res 64:646–653PubMedCrossRef

Titel: Salidroside-Mediated Neuroprotection is Associated with Induction of Early Growth Response Genes (Egrs) Across a Wide Therapeutic Window
verfasst von: Wenfang Lai
Zhenwei Zheng
Xiaoqin Zhang
Yicong Wei
Kedan Chu
John Brown
Guizhu Hong
Lidian Chen
Publikationsdatum: 01.08.2015
Verlag: Springer US
Erschienen in: Neurotoxicity Research / Ausgabe 2/2015
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-015-9529-9

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

25.04.2024 | Hypotonie | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

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

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2015

NMDAR-Mediated Hippocampal Neuronal Death is Exacerbated by Activities of ASIC1a

Impairment of Rat Spatial Learning and Memory in a New Model of Cold Water-Induced Chronic Hypothermia: Implication for Alzheimer’s Disease

Evaluation of Skin Fibroblasts from Amyotrophic Lateral Sclerosis Patients for the Rapid Study of Pathological Features

Mast Cell Serotonin Immunoregulatory Effects Impacting on Neuronal Function: Implications for Neurodegenerative and Psychiatric Disorders

Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

Protective Effect of Spermidine Against Excitotoxic Neuronal Death Induced by Quinolinic Acid in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie