Interaction of AP-1-, AP-2-, and Sp1-like proteins with two distinct sites in the upstream regulatory region of the plasminogen activator inhibitor-1 gene mediates the phorbol 12-myristate 13-acetate response.

Descheemaeker, Koen; Wyns, Sabine; Nelles, Luc; Auwerx, Johan; Ny, Tor; Collen, Désiré

doi:10.1016/s0021-9258(18)42149-7

Cited by 97 publications

(3 citation statements)

References 34 publications

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“…Thus, GC effectiveness is determined by several selective tissue- and/or cell-specific components such as GC bioavailability dependent on metabolizing enzymes notably expression of 11beta-hydroxysteroid dehydrogenase, GR splice variants, contents in GR interacting proteins, and chromatin accessibility [ 24 ]. The PAI-1 promoter is known to have, in addition to GRE, response elements for the AP-1 transcription factor complex (Fos:Jun) [ 70 ]. A plausible explanation of the observed dose-dependent effects is that when moderate levels of activated GR are produced, GR/AP-1 heterodimers, which are known to promote reciprocal transcriptional interference, are mostly formed and prevent PAI-1 transcription through a protein–protein interaction mediated-sequestration process [ 71 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory

et al. 2021

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Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2MAPK signaling cascade strengthens memory. When stress is particularly intense, very high levels of glucocorticoid hormones then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. PAI-1 levels after trauma could be a predictive biomarker of the subsequent appearance of PTSD and pharmacological inhibition of PAI-1 activity a new therapeutic approach to this debilitating condition.

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Section: Discussionmentioning

confidence: 99%

PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory

et al. 2021

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“…PAI-1 can be synthesized and secreted by platelets (Erickson et al, 1985), vascular endothelial cells (Reilly and McFall, 1991), vascular smooth muscle cells (Reilly and McFall, 1991), and several nonvascular cell types (Busso et al, 1994). PAI-1 gene expression can be regulated by a variety of stimuli, including phorbol ester (Descheemaeker et al, 1992), transforming growth factor-b (Sawdey and Loskuto¡, 1991;Song et al, 1998), tumor necrosis factor-a (Sawdey and Los-kuto¡, 1991), interleukin-1 (Bevilacqua et al, 1986), lipopolysaccharide (Crutchley and Conanan, 1986;Sawdey and Loskuto¡, 1991), insulin, and insulin like growth factor-1 (Fattal et al, 1992;Ban¢ et al, 2001), platelet-derived growth factor (Reilly and McFall, 1991), and angiotensin II (Feener et al, 1995;Takeda et al, 2001). Recent studies reported an upregulation of PAI-1 gene expression induced by low oxygen tension (hypoxia) in trophoblast cells (Fitzpatrick and Graham, 1998), hepatocytes (Kietzmann et al, 1999), endothelial cells (Uchiyama et al, 2000), transformed murine macrophages (Pinsky et al, 1998), and some cancer cell lines (Fink et al, 2001).…”

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confidence: 99%

Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts

Zhang

Ann

et al. 2003

Journal of Investigative Dermatology

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Keloids are an excessive accumulation of extracellular matrix. Although numerous studies have shown elevated plasminogen activator inhibitor-1 (PAI-1) levels in keloid fibroblasts compared with those of normal skin. Their specific mechanisms involved in the differential expression of PAI-1 in these cell types. In this study, the upregulation of PAI-1 expression is demonstrated in keloid tissues and their derived dermal fibroblasts, attesting to the persistence, if any, of fundamental differences between in vivo and in vitro paradigms. We further examined the mechanisms involved in hypoxia-induced regulation of PAI-1 gene in dermal fibroblast derived from keloid lesions and associated clinically normal peripheral skins from the same patient. Primary cultures were exposed to an environmental hypoxia or desferroxamine. We found that the hypoxia-induced elevation of PAI-1 gene appears to be regulated at both transcriptional and post-transcriptional levels in keloid fibroblasts. Furthermore, our results showed a consistent elevation of HIF-1alpha protein level in keloid tissues compared with their normal peripheral skin controls, implying a potential role as a biomarker for local skin hypoxia. Treatment with antisense oligonucleotides against hypoxia-inducible factor 1alpha (HIF-1alpha) led to the downregulation of steady-state levels of PAI-1 mRNA under both normoxic and hypoxic conditions. Conceivably, our results suggest that HIF-1alpha may be a novel therapeutic target to modulate the scar fibrosis process.

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“…The PAI-1 inhibitors augment tPA and plasmin activity, and significantly lower plasma and brain Ab levels (Jacobsen et al, 2008). The presence of c-Junresponsive elements in the PAI-1 promoter has been reported (it is an AP-1-like binding site; Descheemaeker et al, 1992). However, DHA inhibits AP-1 and suppresses AP-1 activation (transcription factor activator protein 1; Liu et al, 2001;Zgórzyńska et al, 2021) via PPARɣ (Konstantinopoulos et al, 2007;Fig.…”

Section: The Mechanisms Of Bdnf's Actionmentioning

confidence: 99%

DHA (omega-3 fatty acid) increases the action of brain-derived neurotrophic factor (BDNF)

Majou,

Dermenghem

2024

OCL

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Neurons have high energy needs, requiring a continuous supply of glucose from the blood. Tight regulation of glucose metabolism in response to stimuli is essential for brain physiology. Glucose metabolism and cerebral blood flow are closely coordinated during neuronal activity to maintain proper brain function. In a previous article, we have already detailed the mechanisms by which the PI3K/Akt signaling pathway is involved in the efficiency of glucose uptake by stimulating GLUT-1 action and NO-mediated vasodilation. In this article, we now clarify how the activation of BDNF helps to stimulate the IRS-1/PI3K/Akt signaling pathway and upregulates NMDA receptor activity. In short, high-frequency neuronal activity induces the secretion of BDNF, whose presence boosts this important pathway. DHA, via the PPARα-RXRα and PPARɣ-RXRα heterodimers, is involved in the critical regulation of BDNF activation. As a preferential ligand of PPARs and RXRα, DHA plays an important role in the gene expression of CREB and CPE, and it is involved in the regulation and expression of tPA, as well as the inhibition of PAI-1. BDNF boosts the IGF-1/estradiol/PI3K/Akt signaling pathway, and DHA boosts the action of BDNF.

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Interaction of AP-1-, AP-2-, and Sp1-like proteins with two distinct sites in the upstream regulatory region of the plasminogen activator inhibitor-1 gene mediates the phorbol 12-myristate 13-acetate response.

Cited by 97 publications

References 34 publications

PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory

PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory

Mechanisms of Hypoxic Regulation of Plasminogen Activator Inhibitor-1 Gene Expression in Keloid Fibroblasts

DHA (omega-3 fatty acid) increases the action of brain-derived neurotrophic factor (BDNF)

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