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Title

Retinoids and activation of PKC induce tissue-type plasminogen activator expression and storage in human astrocytes
Authors
Hultman, K.
Tjärnlund-Wolf, A.
Fish, Richard
Wilhelmsson, U.
Rydenhag, B.
Pekny, M.
Kruithof, Egbert
Jern, C.
Published in Journal of Thrombosis and Haemostasis. 2008, vol. 6, no. 10, p. 1796-803
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
Identifiers
PMID: 18647223
Full text
Article (Author postprint) (558 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www3.interscience.wiley.com/cgi-bin/fulltext/120839870/HTMLSTART
Structures
Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research groups Endothélium vasculaire (11)
Bases moléculaires des anomalies génétiques de l'hémostase (504)
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. 1796-803. https://archive-ouverte.unige.ch/unige:2534

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Deposited on : 2009-08-28

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