| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea; and
Department of Biology, College of Natural Sciences, and
Department of Biology, Teacher’s College, Kyungpook National University, Daegu, South Korea
The induction of inducible NO synthase (iNOS) by group IIA phospholipase A2 (PLA2) involves the stimulation of a novel signaling cascade. In this study, we demonstrate that group IIA PLA2 up-regulates the expression of iNOS through a novel pathway that includes M-type secretory PLA2 receptor (sPLA2R), phosphatidylinositol 3-kinase (PI3K), and Akt. Group IIA PLA2 stimulated iNOS expression and promoted nitrite production in a dose- and time-dependent manner in Raw264.7 cells. Upon treating with group IIA PLA2, Akt is phosphorylated in a PI3K-dependent manner. Pretreatment with LY294002, a PI3K inhibitor, strongly suppressed group IIA PLA2-induced iNOS expression and PI3K/Akt activation. The promoter activity of iNOS was stimulated by group IIA PLA2, and this was suppressed by LY294002. Transfection with Akt cDNA resulted in Akt protein overexpression in Raw264.7 cells and effectively enhanced the group IIA PLA2-induced reporter activity of the iNOS promoter. M-type sPLA2R was highly expressed in Raw264.7 cells. Overexpression of M-type sPLA2R enhanced group IIA PLA2-induced promoter activity and iNOS protein expression, and these effects were abolished by LY294002. However, site-directed mutation in residue responsible for PLA2 catalytic activity markedly reduced their ability to production of nitrites and expression of iNOS. These results suggest that group IIA PLA2 induces nitrite production by involving of M-type sPLA2R, which then mediates signal transduction events that lead to PI3K/Akt activation.
This article has been cited by other articles:
|
|
 |
|
  A. Babu, X. Meng, A. M. Banerjee, F. Gamboni-Robertson, J. C. Cleveland, S. Damle, D. A. Fullerton, and M. J. Weyant Secretory phospholipase A(2) is required to produce histologic changes associated with gastroduodenal reflux in a murine model. J. Thorac. Cardiovasc. Surg., June 1, 2008; 135(6): 1220 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Granata, A. Petraroli, E. Boilard, S. Bezzine, J. Bollinger, L. Del Vecchio, M. H. Gelb, G. Lambeau, G. Marone, and M. Triggiani Activation of Cytokine Production by Secreted Phospholipase A2 in Human Lung Macrophages Expressing the M-Type Receptor J. Immunol., January 1, 2005; 174(1): 464 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Jo, H.-Y. Lee, Y.-N. Lee, J. I. Kim, H.-K. Kang, D.-W. Park, S.-H. Baek, J.-Y. Kwak, and Y.-S. Bae Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-{kappa}B in Human Neutrophils J. Immunol., November 15, 2004; 173(10): 6433 - 6439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dahlin, E. M. Mager, L. Allen, Z. Tigue, L. Goodglick, M. Wadehra, and L. Dobbs Identification of Genes Differentially Expressed in Rat Alveolar Type I Cells Am. J. Respir. Cell Mol. Biol., September 1, 2004; 31(3): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. H. Ginzberg, P. T. Shannon, T. Suzuki, O. Hong, E. Vachon, T. Moraes, M. T. H. Abreu, V. Cherepanov, X. Wang, C.-W. Chow, et al. Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G286 - G298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Lim, Y.-A. Choi, W. Park, T. Lee, S. H. Ryu, S.-Y. Kim, J.-R. Kim, J.-H. Kim, and S.-H. Baek Phosphatidic Acid Regulates Systemic Inflammatory Responses by Modulating the Akt-Mammalian Target of Rapamycin-p70 S6 Kinase 1 Pathway J. Biol. Chem., November 14, 2003; 278(46): 45117 - 45127. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
