Role of cytosolic phospholipase A2α in cell rounding and cytotoxicity induced by ceramide-1-phosphate via ceramide kinase

2011 ◽  
Vol 512 (1) ◽  
pp. 45-51 ◽  
Author(s):  
Hiroyuki Nakamura ◽  
Eiko Tada ◽  
Tomohiko Makiyama ◽  
Kana Yasufuku ◽  
Toshihiko Murayama
Keyword(s):  
Cell Rounding ◽  
Ceramide Kinase ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α ◽  
Ceramide 1

scholarly journals Cytosolic Phospholipase A2α–deficient Mice Are Resistant to Collagen-induced Arthritis

2003 ◽  
Vol 197 (10) ◽  
pp. 1297-1302 ◽  
Author(s):  
Martin Hegen ◽  
Linhong Sun ◽  
Naonori Uozumi ◽  
Kazuhiko Kume ◽  
Mary E. Goad ◽  
...  
Keyword(s):  
Critical Role ◽  
Wild Type ◽  
Collagen Induced Arthritis ◽  
Cytosolic Phospholipase ◽  
Severity Scores ◽  
In The Wild ◽  
Cytosolic Phospholipase A2α ◽  
Antibody Levels ◽  
Deficient Mice

Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2α (cPLA2α) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2α plays a key role in the development of CIA, we backcrossed cPLA2α-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA2α-deficient mice compared with wild-type littermates. At completion of the study, >90% of the wild-type mice had developed disease whereas none of the cPLA2α-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA2α-deficient mice. Although the disease scores differed significantly between cPLA2α mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA2α in the pathogenesis of CIA.

Ceramide-1-phosphate activates cytosolic phospholipase A2α directly and by PKC pathway

2006 ◽  
Vol 71 (6) ◽  
pp. 850-857 ◽  
Author(s):  
Hiroyuki Nakamura ◽  
Tetsuya Hirabayashi ◽  
Masaya Shimizu ◽  
Toshihiko Murayama
Keyword(s):  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α ◽  
Ceramide 1

scholarly journals An Essential Role of Cytosolic Phospholipase A2α in Prostaglandin E2–mediated Bone Resorption Associated with Inflammation

2003 ◽  
Vol 197 (10) ◽  
pp. 1303-1310 ◽  
Author(s):  
Chisato Miyaura ◽  
Masaki Inada ◽  
Chiho Matsumoto ◽  
Tomoyasu Ohshiba ◽  
Naonori Uozumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Bone Loss ◽  
Stromal Cells ◽  
Osteoclast Formation ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α ◽  
Cox 2

Prostaglandin E (PGE)2 produced by osteoblasts acts as a potent stimulator of bone resorption. Inflammatory bone loss is accompanied by osteoclast formation induced by bone-resorbing cytokines, but the mechanism of PGE2 production and bone resorption in vivo is not fully understood. Using cytosolic phospholipase A2α (cPLA2α)-null mice, we examined the role of cPLA2α in PGE2 synthesis and bone resorption. In bone marrow cultures, interleukin (IL)-1 markedly stimulated PGE2 production and osteoclast formation in wild-type mice, but not in cPLA2α-null mice. Osteoblastic bone marrow stromal cells induced the expression of cyclooxygenase (COX)-2 and membrane-bound PGE2 synthase (mPGES) in response to IL-1 and lipopolysaccharide (LPS) to produce PGE2. Osteoblastic stromal cells collected from cPLA2α-null mice also induced the expression of COX-2 and mPGES by IL-1 and LPS, but could not produce PGE2 due to the lack of arachidonic acid release. LPS administration to wild-type mice reduced femoral bone mineral density by increased bone resorption. In cPLA2α-null mice, however, LPS-induced bone loss could not be observed at all. Here, we show that cPLA2α plays a key role in PGE production by osteoblasts and in osteoclastic bone resorption, and suggest a new approach to inflammatory bone disease by inhibiting cPLA2α.

scholarly journals Predominant Role of Cytosolic Phospholipase A2α in Dioxin-induced Neonatal Hydronephrosis in Mice

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Wataru Yoshioka ◽  
Tatsuya Kawaguchi ◽  
Nozomi Fujisawa ◽  
Keiko Aida-Yasuoka ◽  
Takao Shimizu ◽  
...  
Keyword(s):  
Predominant Role ◽  
Cytosolic Phospholipase ◽  
Neonatal Hydronephrosis ◽  
Cytosolic Phospholipase A2α

scholarly journals The role of cytosolic phospholipase A2α in amyloid precursor protein induction by amyloid beta1-42: implication for neurodegeneration

2015 ◽  
Vol 132 (5) ◽  
pp. 559-571 ◽  
Author(s):  
Chen Sagy-Bross ◽  
Ksenia Kasianov ◽  
Yulia Solomonov ◽  
Alex Braiman ◽  
Alon Friedman ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α

scholarly journals Lipidomics Revealed Alteration of Sphingolipid Metabolism During the Reparative Phase After Myocardial Infarction Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Tong Hua ◽  
Qiankun Bao ◽  
Xue He ◽  
Wenbin Cai ◽  
Jinlong He
Keyword(s):  
Myocardial Infarction ◽  
Marked Change ◽  
Heart Tissue ◽  
Sphingolipid Metabolism ◽  
Ceramide Kinase ◽  
Inflammatory Phase ◽  
Cardiac Pathophysiology ◽  
The Difference ◽  
Ceramide 1

Aberrant sphingolipid metabolism contributes to cardiac pathophysiology. Emerging evidence found that an increased level of ceramide during the inflammatory phase of post-myocardial infarction (MI) served as a biomarker and was associated with cardiac dysfunction. However, the alternation of the sphingolipid profile during the reparative phase after MI is still not fully understood. Using a mouse model of the left anterior descending ligation that leads to MI, we performed metabolomics studies to assess the alternations of both plasma and myocardial sphingolipid profiles during the reparative phase post-MI. A total number of 193 sphingolipid metabolites were detected. Myocardial sphingolipids but not plasma sphingolipids showed marked change after MI injury. Ceramide-1-phosphates, which were accumulated after MI, contributed highly to the difference in sphingolipid profiles between groups. Consistently, the expression of ceramide kinase, which phosphorylates ceramides to generate ceramide-1-phosphates, was upregulated in heart tissue after MI injury. Our findings revealed the altering sphingolipid metabolism during the reparative phase post-MI and highlighted the potential role of ceramide kinase/ceramide-1-phosphate in ischemic heart disease.

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