Possible roles of arachidonic acid and its metabolites in induction of tissue plasminogen activator (t-PA) production in human fibroblast, IMR-90 cells by proteose peptone

Suzuki, Atsushi; Mitsuda, Shinjiro; Higashio, Kanji; Kumasaka, T

doi:10.1016/0167-4889(92)90065-j

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…It has been known that IMR-90 fibroblasts are constantly producing t-PA and u-PA (23,24). Suzuki et al have found that proteose peptone is a potent inducer for t-PA production by IMR-90 cells and that the induction is closely related to the activation of phospholipase A2 and arachidonate metabolite(s) from lipoxygenase pathway (25)(26)(27). We have previously reported that thrombin increased t-PA mRNA levels in IMR-90 cells (28).…”

Section: Introductionmentioning

confidence: 77%

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

et al. 1995

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SummaryThe mechanism of thrombin induction of tissue- and urokinase-type plasminogen activator (t-PA and u-PA) biosynthesis was investigated in cultured human fetal lung fibroblast cells, IMR-90. Northern blot analysis of total RNA from thrombin-treated cells showed marked accumulations of both t-PA and u-PA mRNA during 24 h. Nuclear run-on experiments showed that the transcription rates of both genes were increased in the thrombin-treated cells.These thrombin effects were inhibited by cycloheximide (CHX), an inhibitor of protein biosynthesis. Treatment of IMR-90 cells with CHX alone caused an increase in u-PA mRNA but not in t-PA mRNA. CHX, however, did not affect the transcription rates of both genes in the cells. Thus, on-going protein synthesis is required for increased accumulations of both t-PA and u-PA mRNA by thrombin but not for the constitutive expression of u-PA gene in IMR-90 cells. Therefore, we conclude that the accumulations of t-PA and u-PA mRNA due to thrombin result mainly from increased rates of their gene transcriptions, and that this influence is exerted in part by proteins synthesized by thrombin stimulation.Thrombin also increased plasminogen activator inhibitor type-1 (PAI-1) in the levels of both antigen and mRNA more rapidly than it increased t-PA in IMR-90 cells. In conditioned medium, most of the secreted PAI-1 seemed to form a complex with t-PA. Northern blot analysis using a PAI-2 cDNA probe showed that the levels of PAI-2 mRNA were markedly increased in response to thrombin. PAI-2 appeared not to have been secreted by the cells because the antigen was rarely detectable in the conditioned medium. Thus, thrombin increases not only plasminogen activators, but their inhibitors as well.

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Section: Introductionmentioning

confidence: 77%

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

et al. 1995

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“…To rule out the effect of an arachidonic acid metabolite, 10 µ m indomethacin (a cyclo‐oxygenase inhibitor; Laneuville et al . 1994) and 100 µ m NDGA (a lipoxygenase inhibitor; Suzuki et al . 1992) were applied to Xenopus oocytes for 5 min, followed immediately by application of 100 µ m arachidonic acid together with 100 µ m glycine.…”

Section: Arachidonic Acid Inhibits Glycine Transportmentioning

confidence: 99%

Arachidonic acid and anandamide have opposite modulatory actions at the glycine transporter, GLYT1a

Pearlman¹,

Aubrey²,

Vandenberg³

2003

Journal of Neurochemistry

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The GLYT1 subtypes of glycine transporter are expressed in glia surrounding excitatory synapses in the mammalian CNS and may regulate synaptic glycine concentrations required for activation of the NMDA subtypes of glutamate receptor. In this report we demonstrate that the rate of glycine transport by GLYT1 is inhibited by arachidonic acid. The cyclo-oxygenase and lipoxygenase inhibitors indomethacin and nordihydroguaiaretic acid, and the protein kinase C inhibitor staurosporine, had no effect on the extent of arachidonic acid inhibition of transport, which suggests that the inhibitory effects of arachidonic acid result from a direct interaction with the transporter. In contrast to arachidonic acid, its amide derivative, anandamide, and the more stable analogue R1-methanandamide stimulate glycine transport. This stimulation is unlikely to be a secondary effect of cannabinoid receptor stimulation because the cannabinoid receptor agonist WIN 55 212-2 had no effect on transport. We suggest that the stimulatory effects of anandamide on GLYT1 are due to a direct interaction with the transporter.

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“…Phospholipase A2 (PLA2 ) and arachidonic acid metabolites have been shown to mediate TNF or IL-1 signal transduction (Parker et al, 1987;Haliday et al, 1991 ;Suzuki et al, 1992) . It was therefore of interest to investigate the regulatory effects of PLA 2 and downstream signal-transduction enzymes on the cytokineinduced activity of PA. We found that the PLA2 inhibitor mepacrine blocked the effects of TNF-a and ILlß on the net PA activity in astrocytes ( Table 2), indicating that PLA2 may be involved in the signal produced by these cytokines.…”

Section: Signal Transduction Pathways Involved In the Cytokine-inducementioning

confidence: 99%

Components of the Plasminogen Activator System in Astrocytes Are Modulated by Tumor Necrosis Factor‐α and Interleukin‐1β Through Similar Signal Transduction Pathways

Faber-Elman¹,

Miskin

Schwartz³

1995

Journal of Neurochemistry

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Migration of astrocytes is thought to play a role in nerve regeneration and to be mediated, at least in part, by inflammation‐associated cytokines. Plasminogen activators are secreted proteases that function in fibrinolysis and participate in cellular migration and invasion and, in some cases, are modulated by cytokines. Here, we show that two cytokines, tumor necrosis factor‐α and interleukin‐1β, can modulate plasminogen activation in astrocytes, each causing 90% reduction of total plasminogen activator activity. Direct and reverse zymography indicated that this reduction resulted from two simultaneous events, a pronounced decrease in tissue‐type plasminogen activator activity and an induction of plasminogen activator inhibitor‐1. Northern hybridization analysis indicated a 30‐fold increase of the steady‐state level of plasminogen activator inhibitor‐1 mRNA following treatment with each of the two cytokines. Both of the cytokine‐induced effects could be blocked by cycloheximide or actinomycin D. When signal transduction pathways were blocked, the results indicated the involvement of reduction in cyclic AMP levels, protein kinase activity, and arachidonic metabolites of the lipoxygenase pathway. The results thus show that the two cytokines reduce the ability of astrocytes to conduct fibrinolysis and extracellular proteolysis, and suggest that the effect of these cytokines on members of the plasminogen activation system is through a common signal transduction pathway.

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Possible roles of arachidonic acid and its metabolites in induction of tissue plasminogen activator (t-PA) production in human fibroblast, IMR-90 cells by proteose peptone

Cited by 5 publications

References 19 publications

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

Transcriptional Regulation of Tissue- and Urokinase-type Plasminogen Activator Genes by Thrombin in Human Fetal Lung Fibroblasts

Arachidonic acid and anandamide have opposite modulatory actions at the glycine transporter, GLYT1a

Components of the Plasminogen Activator System in Astrocytes Are Modulated by Tumor Necrosis Factor‐α and Interleukin‐1β Through Similar Signal Transduction Pathways

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