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Oxidized low-density lipoprotein-induced matrix metalloproteinase-9 expression via PKC-delta/p42/p44 MAPK/Elk-1 cascade in brain astrocytes.

Authors: Wang, HH  Hsieh, HL  Wu, CY  Yang, CM 
Citation: Wang HH, etal., Neurotox Res. 2010 Jan;17(1):50-65. Epub 2009 Jun 25.
Pubmed: (View Article at PubMed) PMID:19554388
DOI: Full-text: DOI:10.1007/s12640-009-9077-2

After ischemic injury to brain, disruption of the blood-brain barrier (BBB) raises the possibility of exposing the central nervous system (CNS) to oxidized low-density lipoprotein (oxLDL), a risk factor implicated in neurodegenerative diseases. Matrix metalloproteinases (MMPs), especially MMP-9, contribute to extracellular matrix (ECM) remodeling during the CNS diseases. However, the molecular mechanisms underlying oxLDL-induced MMP-9 expression in astrocytes remained unclear. Here, we reported that oxLDL induced MMP-9 expression via a PKC-delta/p42/p44 MAPK-dependent Elk-1 activation in rat brain astrocyte (RBA)-1 cells, revealed by gelatin zymography, RT-PCR, and Western blotting analyses. These responses were attenuated by pretreatment with pharmacological inhibitors and transfection with dominant negative mutants. Moreover, Elk-1-mediated MMP-9 gene transcription was confirmed by transfection with an Elk-1 binding site-mutated MMP-9 promoter construct (mt-Ets-MMP9), which blocked oxLDL-stimulated MMP-9 luciferase activity. Understanding the regulatory mechanisms by which oxLDL induced MMP-9 expression in astrocytes might provide a new therapeutic strategy of brain diseases.

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CRRD Object Information
CRRD ID: 2325827
Created: 2010-06-10
Species: All species
Last Modified: 2010-06-10
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.