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Oxidative stress response and trafficking of platelet‐activating factor acetylhydrolase type II (PAFAH‐II)
Author(s) -
Fuzaylova Anastasia G.,
Sedlack Elizabeth M.,
Winget Jason M.,
Bahnson Brian J.
Publication year - 2009
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.23.1_supplement.526.7
Subject(s) - myristoylation , oxidative stress , microbiology and biotechnology , membrane , chemistry , biochemistry , cytoplasm , palmitoylation , intracellular , biology , enzyme , cysteine
Platelet activating factor acetylhydrolase type II (PAFAH‐II) is a member of the phospholipase A2 subfamily that can hydrolyze and inactivate platelet activating factor and oxidatively fragmented phospholipids at the sn‐2 position. This enzyme is a 44kDa, intracellular, myristoylated protein that becomes associated with the inner membranes under oxidative stress, thus maintaining cell membrane integrity. In order to elucidate the precise mechanism of the stress response and trafficking of this protein, the role of the myristoyl tail was investigated. Trafficking of myristoylated, wild type PAFAH‐II, and of a mutant (Gly‐2‐Ala) that cannot be myristoylated, was monitored in live cells using fluorescent protein fusion tags. Confocal microscopy indicates that unmyristoylated PAFAH‐II remains cytoplasmic under both stressed and unstressed conditions. In contrast, myristoylated PAFAH‐II, which is only partially localized to the inner membranes prior to stress, becomes more concentrated in the inner membranes upon stress. Therefore, this study shows that the myristoyl tail plays a key role in this oxidative stress response. The possible roles of additional regulatory mechanisms, such as residue modifications, which may be facilitating the exposure of the myristoyl tail for membrane anchoring, are also the focus of our current investigations. Support: COBRE 2P20RR015588 and 1R01HL084366