RGD Reference Report - The anti-fibrinolytic SERPIN, plasminogen activator inhibitor 1 (PAI-1), is targeted to and released from catecholamine storage vesicles. - Rat Genome Database

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The anti-fibrinolytic SERPIN, plasminogen activator inhibitor 1 (PAI-1), is targeted to and released from catecholamine storage vesicles.

Authors: Jiang, Q  Gingles, NA  Olivier, MA  Miles, LA  Parmer, RJ 
Citation: Jiang Q, etal., Blood. 2011 Jun 30;117(26):7155-63. doi: 10.1182/blood-2010-05-287672. Epub 2011 May 19.
RGD ID: 8547918
Pubmed: PMID:21596853   (View Abstract at PubMed)
PMCID: PMC3143556   (View Article at PubMed Central)
DOI: DOI:10.1182/blood-2010-05-287672   (Journal Full-text)

Recent studies suggest a crucial role for plasminogen activator inhibitor-1 (PAI-1) in mediating stress-induced hypercoagulability and thrombosis. However, the mechanisms by which PAI-1 is released by stress are not well-delineated. Here, we examined catecholaminergic neurosecretory cells for expression, trafficking, and release of PAI-1. PAI-1 was prominently expressed in PC12 pheochromocytoma cells and bovine adrenomedullary chromaffin cells as detected by Northern blotting, Western blotting, and specific PAI-1 ELISA. Sucrose gradient fractionation studies and immunoelectron microscopy demonstrated localization of PAI-1 to catecholamine storage vesicles. Secretogogue stimulation resulted in corelease of PAI-1 with catecholamines. Parallel increases in plasma PAI-1 and catecholamines were observed in response to acute sympathoadrenal activation by restraint stress in mice in vivo. Reverse fibrin zymography demonstrated free PAI-1 in cellular releasates. Detection of high molecular weight complexes by Western blotting, consistent with PAI-1 complexed with t-PA, as well as bands consistent with cleaved PAI-1, suggested that active PAI-1 was present. Modulation of PAI-1 levels by incubating PC12 cells with anti-PAI-1 IgG caused a marked decrease in nicotine-mediated catecholamine release. In summary, PAI-1 is expressed in chromaffin cells, sorted into the regulated pathway of secretion (into catecholamine storage vesicles), and coreleased, by exocytosis, with catecholamines in response to secretogogues.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Serpine1Ratcellular response to metal ion  IEP bariumRGD 
Serpine1Ratcellular response to nerve growth factor stimulus  IEP  RGD 
Serpine1Ratcellular response to nicotine  IEP  RGD 
Serpine1Ratcellular response to potassium ion  IEP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Serpine1Ratchromaffin granule  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)


Additional Information