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Mechanisms underlying oxidized low‐density lipoprotein‐induced matrix metalloproteinase‐9 expression in astrocytes
Author(s) -
Wang HuiHsin,
Yang ChuenMao
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a397-d
Subject(s) - matrix metalloproteinase , mapk/erk pathway , protein kinase b , chemistry , blot , western blot , astrocyte , phosphorylation , rottlerin , pi3k/akt/mtor pathway , microbiology and biotechnology , signal transduction , protein kinase c , cancer research , biochemistry , biology , endocrinology , central nervous system , gene
Oxidized low‐density lipoprotein (oxLDL) is a risk factor in many inflammatory diseases. OxLDL is elevated and may induce matrix metalloproteinases (MMPs) expression in the region of brain injury and neurodegenerative diseases. However, the signaling mechanisms underlying oxLDL‐induced MMP‐9 expression in astrocytes remain unclear. First, gelatin zymography, RT‐PCR, and Western blotting analyses showed that oxLDL induced MMP‐9 mRNA and protein expression and stimulated p42/p44 MAPK and Akt phosphorylation. These responses were attenuated by pharmacological inhibitors rottlerin, U0126, LY294002, and transfection with dominant negative mutants. Moreover, oxLDL‐induced MMP‐9 expression was mediated through NF‐κB and AP‐1 which were blocked by helenalin and curcumin, respectively. These results suggest that in astrocytes, oxLDL‐induced MMP‐9 expression was sequentially mediated through PKC‐δ, p42/p44 MAPK and Akt linking to NF‐κB and AP‐1. Understanding the regulation of MMP‐9 expression induced by oxLDL in astrocytes might provide a new therapeutic strategy of brain injury, inflammatory, and neurodegenerative diseases.