Reactive oxygen species upregulate expression of PAI-1 in endothelial cells

• Autorzy: Swiatkowska M. , Szemraj J. , Al-Nedawi K. N. I. , Pawlowska Z.
• Języki publikacji: EN

Abstrakty

EN

Second messengers involved in the signal transduction pathway leading to induction of the plasminogen activator inhibitor (PAI-1) have not yet been well characterized. This study focuses on the mechanisms of regulation of PAI-1 expression by reactive oxygen species (ROS) in human endothelial cells. Inhibition of the tumor necrosis factor α (TNFα)-induced expression of PAI-1 by antioxidant N-acetyl-L-cysteine (NAC) indicated redox-sensitive mechanisms involved in the signalling pathway. Because TNFα induces PAI-1 production in endothelial cells, and NAC attenuated this response, we attempted to investigate the possible involvement of ROS in the activation of PAI-1 by TNFα. Upregulation of PAI-1 expression in endothelial cells by the stimulation with TNFα (50ng/ml) or H2O2 (10-200µM), observed by measurement of the antigen and mRNA levels, was reversed in the presence of NAC (20mM). The stimulatory effect of ROS was detected also at the level of the PAI-1 promoter in endothelial cells transfected with plasmid p800 LUC containing a PAI-1 promoter fragment (+71 to -800). The PAI-1 promoter activity was increased in the presence of ROS, and was suppressed by up to 75% in the presence of antioxidants [1], On the basis of this study we can conclude that reactive oxygen species play an important role in a cytokine-induced activation of PAI-1 expression, and may act as a signal transduction messenger.

Słowa kluczowe

EN

reactive oxygen species; expression; plasminogen activator inhibitor; endothelial cell

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2002
• Tom: 07
• Numer: 4
• Opis fizyczny: p.1065-1071,fig.,ref.

Twórcy

autor

Swiatkowska M.

• Department of Molecular and Medical Biophysics, Medical University of Lodz, Lodz, Poland

autor

Szemraj J.

• Department of Biochemistry, Medical University of Lodz, Lodz, Poland

autor

Al-Nedawi K. N. I.

• Department of Biogenic Amines, Polish Academy of Sciences, Lodz, Poland

autor

Pawlowska Z.

• Department of Molecular and Medical Biophysics, Medical University of Lodz, Lodz, Poland

Bibliografia

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