Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advanced glycation end products (AGEs) and their interaction with the receptor for advanced glycation end products (RAGE) play an important role in diabetic vascular complications. The current study demonstrated that AGEs significantly increased RAGE expression and the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) in human umbilical vein endothelial cell-derived line ECV304 cells. RAGE antisense RNA partially inhibited the expression of TNF-alpha and IL-6 induced by AGEs. Oligonucleotide microarray was used to identify the genes that respond to RAGE activation. Phospholipase C beta 1 (PLC beta 1), phospholipase C beta 4 (PLC beta 4) and calcium/calmodulin-dependent protein kinase IV (CAMK IV) which associated with Ca(2+) signaling were upregulated. The rise of intracellular calcium and the NF-kappaB promoter activity induced by AGEs were suppressed by RAGE antisense RNA, PLC inhibitor U73122 and dominant negative CAMK IV, respectively. These findings suggest that PLC/CAMK IV-NF-kappaB is involved in RAGE mediated signaling pathway in human endothelial cells.
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PMID:PLC/CAMK IV-NF-kappaB involved in the receptor for advanced glycation end products mediated signaling pathway in human endothelial cells. 2017 Dec 62

Intracerebral accumulation of amyloid-beta (A beta) leading to A beta plaque formation, is the main hallmark of Alzheimer's disease and might be caused by defective A beta-clearance. We previously found primary human astrocytes and microglia able to bind and ingest A beta 1-42 in vitro, which appeared to be limited by A beta 1-42 fibril formation. We now confirm that astrocytic A beta-uptake depends on size and/or composition of A beta-aggregates as astrocytes preferably take up oligomeric A beta over fibrillar A beta. Upon exposure to either fluorescence-labelled A beta 1-42 oligomers (A beta(oligo)) or fibrils (A beta(fib)), a larger (3.7 times more) proportion of astrocytes ingested oligomers compared to fibrils, as determined by flow cytometry. A beta-internalization was verified using confocal microscopy and live-cell imaging. Neither uptake of A beta(oligo) nor A beta(fib), triggered proinflammatory activation of the astrocytes, as judged by quantification of interleukin-6 and monocyte-chemoattractant protein-1 release. Amyloid-associated proteins, including alpha1-antichymotrypsin (ACT), serum amyloid P component (SAP), C1q and apolipoproteins E (ApoE) and J (ApoJ) were earlier found to influence A beta-aggregation. Here, astrocytic uptake of A beta(fib) increased when added to the cells in combination with SAP and C1q (SAP/C1q), but was unchanged in the presence of ApoE, ApoJ and ACT. Interestingly, ApoJ and ApoE dramatically reduced the number of A beta(oligo)-positive astrocytes, whereas SAP/C1q slightly reduced A beta(oligo) uptake. Thus, amyloid-associated proteins, especially ApoJ and ApoE, can alter A beta-uptake in vitro and hence may influence A beta clearance and plaque formation in vivo.
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PMID:Astrocytic A beta 1-42 uptake is determined by A beta-aggregation state and the presence of amyloid-associated proteins. 2054 59


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