| pubmed-article:12621026 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C0040048 | lld:lifeskim |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C1514559 | lld:lifeskim |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C1415761 | lld:lifeskim |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C1708295 | lld:lifeskim |
| pubmed-article:12621026 | lifeskim:mentions | umls-concept:C0061421 | lld:lifeskim |
| pubmed-article:12621026 | pubmed:issue | 19 | lld:pubmed |
| pubmed-article:12621026 | pubmed:dateCreated | 2003-5-5 | lld:pubmed |
| pubmed-article:12621026 | pubmed:abstractText | Previous studies have demonstrated that overexpression of GRP78/BiP, an endoplasmic reticulum (ER)-resident molecular chaperone, in mammalian cells inhibits the secretion of specific coagulation factors. However, the effects of GRP78/BiP on activation of the coagulation cascade leading to thrombin generation are not known. In this study, we examined whether GRP78/BiP overexpression mediates cell surface thrombin generation in a human bladder cancer cell line T24/83 having prothrombotic characteristics. We report here that cells overexpressing GRP78/BiP exhibited significant decreases in cell surface-mediated thrombin generation, prothrombin consumption and the formation of thrombin-inhibitor complexes, compared with wild-type or vector-transfected cells. This effect was attributed to the ability of GRP78/BiP to inhibit cell surface tissue factor (TF) procoagulant activity (PCA) because conversion of factor X to Xa and factor VII to VIIa were significantly lower on the surface of GRP78/BiP-overexpressing cells. The additional findings that (i) cell surface factor Xa generation was inhibited in the absence of factor VIIa and (ii) TF PCA was inhibited by a neutralizing antibody to human TF suggests that thrombin generation is mediated exclusively by TF. GRP78/BiP overexpression did not decrease cell surface levels of TF, suggesting that the inhibition in TF PCA does not result from retention of TF in the ER by GRP78/BiP. The additional observations that both adenovirus-mediated and stable GRP78/BiP overexpression attenuated TF PCA stimulated by ionomycin or hydrogen peroxide suggest that GRP78/BiP indirectly alters TF PCA through a mechanism involving cellular Ca(2+) and/or oxidative stress. Similar results were also observed in human aortic smooth muscle cells transfected with the GRP78/BiP adenovirus. Taken together, these findings demonstrate that overexpression of GRP78/BiP decreases thrombin generation by inhibiting cell surface TF PCA, thereby suppressing the prothrombotic potential of cells. | lld:pubmed |
| pubmed-article:12621026 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12621026 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12621026 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12621026 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12621026 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12621026 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12621026 | pubmed:month | May | lld:pubmed |
| pubmed-article:12621026 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:MeeSS | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:BerryLeslie... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:ChanAnthony... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:KlamutHenry... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:DickhoutJeffr... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:LingXuX | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:AustinRichard... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:WerstuckGeoff... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:BajzarLaszloL | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:WatsonLindsay... | lld:pubmed |
| pubmed-article:12621026 | pubmed:author | pubmed-author:SoodSudesh... | lld:pubmed |
| pubmed-article:12621026 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12621026 | pubmed:day | 9 | lld:pubmed |
| pubmed-article:12621026 | pubmed:volume | 278 | lld:pubmed |
| pubmed-article:12621026 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12621026 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12621026 | pubmed:pagination | 17438-47 | lld:pubmed |
| pubmed-article:12621026 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:meshHeading | pubmed-meshheading:12621026... | lld:pubmed |
| pubmed-article:12621026 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12621026 | pubmed:articleTitle | Overexpression of the 78-kDa glucose-regulated protein/immunoglobulin-binding protein (GRP78/BiP) inhibits tissue factor procoagulant activity. | lld:pubmed |
| pubmed-article:12621026 | pubmed:affiliation | Department of Pathology, McMaster University, Hamilton, Ontario L8V 1C3, Canada. | lld:pubmed |
| pubmed-article:12621026 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12621026 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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