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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.
Wilhelmsson, U.
Rydenhag, B.
Pekny, M.
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/metabolismBrain ChemistryEnzyme Activation/drug effectsGene Expression RegulationHumansKineticsProtein Kinase C/metabolismRNA, Messenger/analysisRetinoids/pharmacologyTetradecanoylphorbol Acetate/pharmacologyTissue Plasminogen Activator/genetics/metabolism/secretion
Identifiers
PMID: 18647223
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Structures
Research groups Endothélium vasculaire (11)
Recherche translationnelle : anomalies de l'hémostase et thromboses (504)
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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. doi: 10.1111/j.1538-7836.2008.03084.x https://archive-ouverte.unige.ch/unige:2534

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Deposited on : 2009-08-28

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