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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.
Pubmed: (View Article at PubMed) PMID:21596853
DOI: Full-text: DOI:10.1182/blood-2010-05-287672

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.

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CRRD Object Information
CRRD ID: 8547918
Created: 2014-02-28
Species: All species
Last Modified: 2014-02-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.