Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal glomerular microvascular endothelial cell damage is characteristic of Shiga toxin-associated hemolytic uremic syndrome (HUS). An impaired renal fibrinolysis may be responsible for renal microvascular fibrin accumulation during the course of HUS disease. This study examined the effect of Shiga toxin, bacterial lipopolysaccharide (LPS, endotoxin), and tumor necrosis factor (TNF) on the expression of fibrinolysis factors by human renal glomerular microvascular endothelial cells (HRMEC) in vitro. The results were compared to a previously better-characterized endothelial cell type, human umbilical vein endothelial cells (HUVEC). In HUVEC, the ratio of fibrinolysis antigens was antifibrinolytic, consisting of 55-fold more plasminogen activator inhibitor type 1 (PAI-1) than tissue-type plasminogen activator (tPA). Treatment of HUVEC with LPS or TNF accentuated this ratio by decreasing tPA and increasing PAI-1 expression. In contrast, HRMEC produced urokinase-type plasminogen activator (uPA) in a 24-fold excess to PAI-1 and were thereby profibrinolytic with regard to fibrinolysis antigen expression. LPS and TNF further decreased PAI-1 antigen expression by HRMEC. These results argue against a role for LPS or TNF in decreasing renal fibrinolysis at the level of fibrinolysis factor expression by renal endothelial cells. Nevertheless, HUVEC and HRMEC were responsive to the same LPS analogs in the same order of potency. Shiga toxin decreased fibrinolysis factor expression to a greater extent in HRMEC than in HUVEC. Since HRMEC fibrinolysis antigen expression was profibrinolytic, the Shiga toxin-mediated decrease in renal endothelial uPA synthesis may predispose renal microvasculature to thrombosis and may have implications for the development of HUS.
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PMID:Human renal microvascular endothelial cells as a potential target in the development of the hemolytic uremic syndrome as related to fibrinolysis factor expression, in vitro. 808 1

The mammalian intracellular phospholipase A(1) (iPLA(1)) family consists of three members, iPLA(1)alpha/PA-PLA(1), iPLA(1)beta/p125, and iPLA(1)gamma/KIAA0725p. Although iPLA(1)beta has been implicated in organization of the ER-Golgi compartments, little is known about the physiological role of its closest paralog, iPLA(1)gamma. Here we show that iPLA(1)gamma mediates a specific retrograde membrane transport pathway between the endoplasmic reticulum (ER) and the Golgi complex. iPLA(1)gamma appeared to be localized to the cytosol, the cis-Golgi, and the ER-Golgi intermediate compartment (ERGIC). Time-lapse microscopy revealed that a population of GFP-iPLA(1)gamma was associated with transport carriers moving out from the Golgi complex. Knockdown of iPLA(1)gamma expression by RNAi did not affect the anterograde transport of VSVGts045 but dramatically delayed two types of Golgi-to-ER retrograde membrane transport; that is, transfer of the Golgi membrane into the ER in the presence of brefeldin A and delivery of cholera toxin B subunit from the Golgi complex to the ER. Notably, knockdown of iPLA(1)gamma did not impair COPI- and Rab6-dependent retrograde transports represented by ERGIC-53 recycling and ER delivery of Shiga toxin, respectively. Thus, iPLA(1)gamma is a novel membrane transport factor that contributes to a specific Golgi-to-ER retrograde pathway distinct from presently characterized COPI- and Rab6-dependent pathways.
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PMID:Intracellular phospholipase A1gamma (iPLA1gamma) is a novel factor involved in coat protein complex I- and Rab6-independent retrograde transport between the endoplasmic reticulum and the Golgi complex. 1963 84