title: Tanshinone IIA dampens the cell proliferation induced by ischemic insult in rat astrocytes via blocking the activation of HIF-1α/SDF-1 signaling.
abstract: OBJECTIVE
  Tanshinone IIA (TSA) has been reported to protect neurons and microvascular endothelial cells against ischemic injury. However, the effect of TSA on astrocytes in response to ischemic injury is not clear. The aims of this study were to evaluate the effect of TSA on astrocytes following ischemic insult.
  
  
  METHODS
  Primary cultured rat astrocytes were treated with oxygen-glucose deprivation (OGD) followed by recovery. Cell death was measured by lactate dehydrogenase assay. Astrocyte proliferation was determined by cell viability assay, cell counting and 5-bromo-2-deoxyuridine incorporation assay. The glial fibrillary acidic protein (GFAP) expression was assessed by immunocytochemistry. Stromal cell-derived factor-1 (SDF-1) secretion from astrocytes was measured by enzyme linked immunosorbent assay. The expressions of hypoxia inducible factor-1α (HIF-1α), SDF-1, GFAP and the phosphorylation of Akt and extracellular regulated protein kinase (Erk) 1/2 were evaluated by immunoblot assay. Quantitative RT-PCR was used to assess the mRNA expression of HIF-1α and SDF-1.
  
  
  RESULTS
  Mild OGD (2 h-OGD) did not induce astrocyte injury but proliferation at 48 and 72 h after recovery. Mild OGD also induced the accumulation of HIF-1α, the subsequent expression and secretion of SDF-1, resulting in the phosphorylation of Erk1/2 and Akt. TSA attenuated astrocyte proliferation and significantly decreased the OGD-induced accumulation of HIF-1α and SDF-1, then blocked the downstream signaling, Erk1/2 and Akt activation.
  
  
  CONCLUSIONS
  TSA inhibits the astrocyte proliferation induced by sub-lethal ischemic insult via blocking the activation of HIF-1α/SDF-1 pathway. This finding suggests that TSA may be a potential therapeutic option for gliosis after cerebral ischemia.
authors: Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China. Electronic address: huangxj2008@hotmail.com.
authors: Xiaojia
authors: X
authors: Huang
authors: Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Yongjin
authors: Y
authors: Li
authors: Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Jing
authors: J
authors: Li
authors: Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Yun
authors: Y
authors: Feng
authors: Department of Pharmacology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
authors: Xiao
authors: X
authors: Xu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D005904:Glial Fibrillary Acidic Protein; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C021751:tanshinone; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose
keywords: Astrocytes; Hypoxia inducible factor-1α; Ischemia; Stromal cell-derived factor-1; Tanshinone IIA