15-deoxy-Δ12,14-prostaglandin J2 impairs phosphatidylcholine synthesis and induces nuclear accumulation of thiol-modified cytidylyltransferase

被引：10

作者：

Ryan, Alan J. ^{[2
]}

Chen, Bill B.

Vennalaganti, Prashanth R. ^{[1
]}

Henderson, Florita C. ^{[2
]}

Tephly, Linda A. ^{[2
]}

Carter, A. Brent ^{[1
,2
]}

Mallampalli, Rama K. ^{[1
,2
]}

机构：

[1] Univ Iowa, Vet Affairs Med Ctr, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA

[2] Univ Iowa, Dept Internal Med, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 36期

关键词：

D O I：

10.1074/jbc.M801167200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Synthesis of phosphatidylcholine, the major phospholipid of animal cell membranes, requires the key enzyme cytidylyltransferase (CCT alpha). Cysteine sulfhydryls within CCT alpha are needed for full catalytic activity. Here we show that prostaglandin 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) inactivates CCT alpha by inducing generation of reactive oxidant species and the appearance of a cross-linked CCT alpha dimer in cells. N-Acetyl-L-cysteine reduced oxidative stress, prevented CCT alpha cross-linking, and restored CCT function in 15d-PGJ(2)-treated cells. 15d-PGJ(2) modified critical cysteine residues within CCT alpha as determined by mutagenesis studies and by incorporation of biotin-15d-PGJ(2) into CCT alpha. These effects of 15d-PGJ(2) were associated with CCT alpha accumulation within the nucleus. The data indicate that bioactive prostanoids significantly impair membrane phospholipid production by promoting cysteine cross-bridging within CCT alpha.

引用

页码：24628 / 24640

页数：13

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