scholarly journals Ceramide 1-Phosphate Acts as a Positive Allosteric Activator of Group IVA Cytosolic Phospholipase A2α and Enhances the Interaction of the Enzyme with Phosphatidylcholine

2005 ◽  
Vol 280 (18) ◽  
pp. 17601-17607 ◽  
Author(s):  
Preeti Subramanian ◽  
Robert V. Stahelin ◽  
Zdzislaw Szulc ◽  
Alicja Bielawska ◽  
Wonhwa Cho ◽  
...  
2009 ◽  
Vol 284 (39) ◽  
pp. 26897-26907 ◽  
Author(s):  
Nadia F. Lamour ◽  
Preeti Subramanian ◽  
Dayanjan S. Wijesinghe ◽  
Robert V. Stahelin ◽  
Joseph V. Bonventre ◽  
...  

2006 ◽  
Vol 71 (6) ◽  
pp. 850-857 ◽  
Author(s):  
Hiroyuki Nakamura ◽  
Tetsuya Hirabayashi ◽  
Masaya Shimizu ◽  
Toshihiko Murayama

2007 ◽  
Vol 282 (28) ◽  
pp. 20467-20474 ◽  
Author(s):  
Robert V. Stahelin ◽  
Preeti Subramanian ◽  
Mohsin Vora ◽  
Wonhwa Cho ◽  
Charles E. Chalfant

2019 ◽  
Vol 12 (610) ◽  
pp. eaav5918 ◽  
Author(s):  
H. Patrick MacKnight ◽  
Daniel J. Stephenson ◽  
L. Alexis Hoeferlin ◽  
Savannah D. Benusa ◽  
James T. DeLigio ◽  
...  

The sphingolipid ceramide 1-phosphate (C1P) directly binds to and activates group IVA cytosolic phospholipase A2 (cPLA2α) to stimulate the production of eicosanoids. Because eicosanoids are important in wound healing, we examined the repair of skin wounds in knockout (KO) mice lacking cPLA2α and in knock-in (KI) mice in which endogenous cPLA2α was replaced with a mutant form having an ablated C1P interaction site. Wound closure rate was not affected in the KO or KI mice, but wound maturation was enhanced in the KI mice compared to that in wild-type controls. Wounds in KI mice displayed increased infiltration of dermal fibroblasts into the wound environment, increased wound tensile strength, and a higher ratio of type I:type III collagen. In vitro, primary dermal fibroblasts (pDFs) from KI mice showed substantially increased collagen deposition and migration velocity compared to pDFs from wild-type and KO mice. KI mice also showed an altered eicosanoid profile of reduced proinflammatory prostaglandins (PGE2 and TXB2) and an increased abundance of certain hydroxyeicosatetraenoic acid (HETE) species. Specifically, an increase in 5-HETE enhanced dermal fibroblast migration and collagen deposition. This gain-of-function role for the mutant cPLA2α was also linked to the relocalization of cPLA2α and 5-HETE biosynthetic enzymes to the cytoplasm and cytoplasmic vesicles. These findings demonstrate the regulation of key wound-healing mechanisms in vivo by a defined protein-lipid interaction and provide insights into the roles that cPLA2α and eicosanoids play in orchestrating wound repair.


2011 ◽  
Vol 512 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Hiroyuki Nakamura ◽  
Eiko Tada ◽  
Tomohiko Makiyama ◽  
Kana Yasufuku ◽  
Toshihiko Murayama

2012 ◽  
Vol 697 (1-3) ◽  
pp. 144-151 ◽  
Author(s):  
Tomohiko Makiyama ◽  
Hiroyuki Nakamura ◽  
Atsushi Nishida ◽  
Toshihiko Murayama

2008 ◽  
Vol 283 (45) ◽  
pp. 31227-31236 ◽  
Author(s):  
John E. Burke ◽  
Yuan-Hao Hsu ◽  
Raymond A. Deems ◽  
Sheng Li ◽  
Virgil L. Woods ◽  
...  

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