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 language | English |
|---|---|
| Pages (from-to) | 59-70 |
| Number of pages | 12 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 112 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2011 Jan 1 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
}
Oxidative stress-induced attenuation of thrombospondin-1 expression in primary rat Astrocytes. / Chen, Jen Kun; Zhan, Yan Jie; Yang, Chung Shi; Tzeng, Shun-Fen.
In: Journal of Cellular Biochemistry, Vol. 112, No. 1, 01.01.2011, p. 59-70.Research output: Contribution to journal › Article
TY - JOUR
T1 - Oxidative stress-induced attenuation of thrombospondin-1 expression in primary rat Astrocytes
AU - Chen, Jen Kun
AU - Zhan, Yan Jie
AU - Yang, Chung Shi
AU - Tzeng, Shun-Fen
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78651332826&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651332826&partnerID=8YFLogxK
U2 - 10.1002/jcb.22732
DO - 10.1002/jcb.22732
M3 - Article
VL - 112
SP - 59
EP - 70
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 1
ER -