Oxidative stress-induced attenuation of thrombospondin-1 expression in primary rat Astrocytes

Jen Kun Chen, Yan Jie Zhan, Chung Shi Yang, Shun Fen Tzeng

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Astrocytes, the major glial population in the central nervous system (CNS), can secrete thrombospondin (TSP)-1 that plays the role in synaptogenesis and axonal sprouting during CNS development and tissue repair. However, little is known about the regulation of TSP-1 expression in astrocytes under oxidative stress condition. Here, a hypoxic mimetic reagent, cobalt chloride (CoCl 2), was used to initiate hypoxia-induced oxidative stress in primary rat astrocytes. CoCl2 at the concentration range of 0.1-0.5mM was found to cause no significant cell death in primary rat astrocytes. However, CoCl2 at 0.2-0.5mM increased intracellular reactive oxygen species (ROS) levels and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression that is known as a hallmark for oxidative damage. We further found that TSP-1 mRNA expression in astrocytes was inhibited dose- and time-dependently by CoCl2. TSP-1 mRNA levels were increased in CoCl2- exposed astrocytes in the presence of the inhibitors (U0126 and PD98059) of mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK), when compared to that detected in the culture only exposed to CoCl2. Moreover, the inhibition in TSP-1 mRNA expression by CoCl2 was blocked by the addition of the potent antioxidant, N-acetylcysteine (NAC). Thus, we conclude that CoCl2 inhibits TSP-1 mRNA expression in astrocytes via a ROS mechanism possibly involving MAPK/ERK. This inhibition may occur after CNS injury and impair the supportive function of astrocytes on neurite growth in the injured CNS tissues.

Original languageEnglish
Pages (from-to)59-70
Number of pages12
JournalJournal of Cellular Biochemistry
Volume112
Issue number1
DOIs
Publication statusPublished - 2011 Jan 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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