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Scientific article
English

Retinoids and activation of PKC induce tissue-type plasminogen activator expression and storage in human astrocytes

Contributors

Hultman, K.; Tjärnlund-Wolf, A.; Fish, Richard; Wilhelmsson, U.; Rydenhag, B.; Pekny, M.; Kruithof, Egbert; Jern, C.

Published in

Journal of thrombosis and haemostasis, vol. 6, no. 10, p. 1796-1803

Publication date

2008

Abstract

BACKGROUND: Emerging data demonstrate important roles for tissue-type plasminogen activator (t-PA) in the central nervous system (CNS). In contrast to endothelial cells, little is known about the regulation of t-PA gene expression and secretion in astrocytes. OBJECTIVES: The aims of the present study were to investigate whether t-PA gene expression is regulated by retinoids and the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) in human astrocytes, and to study whether t-PA is stored and subject to regulated release from these cells, as with endothelial cells. METHODS: Native human astrocytes were treated with RA and/or PMA. mRNA was quantified by real-time RT-PCR and protein secretion determined by ELISA. Intracellular t-PA immunoreactivity in astrocytes was examined by immunocyto- and histochemistry. RESULTS: RA and/or PMA induced a time-dependent increase in t-PA mRNA and protein levels in astrocytes, reaching 10-fold after combined treatment. This was associated with increased amounts of t-PA storage in intracellular granular structures. Both forskolin and histamine induced regulated release of t-PA. The presence of t-PA in reactive astrocytes was confirmed in human brain tissue. CONCLUSIONS: These data show that RA and PKC activation induce a strong up-regulation of t-PA expression in astrocytes, and increased intracellular storage pools. Moreover, a regulated release of t-PA can be induced from these cells. This raises the possibility that astrocytes contribute to the regulation of extracellular t-PA levels in the CNS.

Keywords

  • Astrocytes/metabolism
  • Brain Chemistry
  • Enzyme Activation/drug effects
  • Gene Expression Regulation
  • Humans
  • Kinetics
  • Protein Kinase C/metabolism
  • RNA, Messenger/analysis
  • Retinoids/pharmacology
  • Tetradecanoylphorbol Acetate/pharmacology
  • Tissue Plasminogen Activator/genetics/metabolism/secretion

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

HULTMAN, K. et al. Retinoids and activation of PKC induce tissue-type plasminogen activator expression and storage in human astrocytes. In: Journal of thrombosis and haemostasis, 2008, vol. 6, n° 10, p. 1796–1803. doi: 10.1111/j.1538-7836.2008.03084.x

Main files (1)

Article (Accepted version)

Identifiers

Journal ISSN

1538-7836
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Technical informations

Creation

28/08/2009 10:39:00

First validation

28/08/2009 10:39:00

Update

14/03/2023 15:11:01

Status update

14/03/2023 15:11:01

Last indexation

29/10/2024 11:56:03
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