scholarly journals Roles of Rac and p38 kinase in the activation of cytosolic phospholipase A2 in response to PMA

2005 ◽  
Vol 388 (2) ◽  
pp. 527-535 ◽  
Author(s):  
Hye Jin YOU ◽  
Chang-Hoon WOO ◽  
Eun-Young CHOI ◽  
Sung-Hoon CHO ◽  
Yung Joon YOO ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Dependent Manner ◽  
Perinuclear Region ◽  
P38 Kinase ◽  
Cytosolic Phospholipase ◽  
Cpla2 Activation ◽  
Kinase Cascade ◽  
Cytosolic Pla2 ◽  
Dependent Pathway

The roles of Rac and p38 kinase in the activation of cPLA2 (cytosolic PLA2) in Rat-2 fibroblasts were investigated. In the present study, we found that PMA activates cPLA2 by a Rac-p38 kinase-dependent pathway. Consistent with this, Rac, if activated, was shown to stimulate cPLA2 in a p38 kinase-dependent manner. In another experiment to understand the signalling mechanism by which the Rac-p38 kinase cascade mediates cPLA2 activation in response to PMA, we observed that PMA-induced cPLA2 translocation to the perinuclear region is completely inhibited by the expression of Rac1N17 or treatment with SB203580 (inhibitor of p38 kinase), suggesting that Rac-p38 kinase cascade acts in this instance by mediating the translocation of cPLA2. The mediatory role of p38 kinase in cPLA2 activation was further demonstrated after a treatment with anisomycin, a very effective activator of p38 kinase. Consistent with the mediatory role of p38 kinase in stimulating cPLA2, anisomycin induced the translocation and activation of cPLA2 in a p38 kinase-dependent manner.

scholarly journals Induction of cytosolic phospholipase A2 activity by phosphatidic acid and diglycerides in permeabilized human neutrophils: interrelationship between phospholipases D and A2

1997 ◽  
Vol 322 (2) ◽  
pp. 353-363 ◽  
Author(s):  
Sue A. BAULDRY ◽  
Rhonda E. WOOTEN
Keyword(s):  
Phosphatidic Acid ◽  
Phospholipase A2 ◽  
Second Messengers ◽  
Platelet Activating Factor ◽  
Human Neutrophils ◽  
Partial Restoration ◽  
Permeabilized Cells ◽  
Cpla2 Activation ◽  
Factor Α ◽  
Cytosolic Pla2

Relationships between phospholipases are poorly understood, but phosphatidic acid (PA) and diglycerides (DGs), produced by phospholipase D (PLD) and phosphatidate phosphohydrolase actions, might function as second messengers coupling cell stimulation to cellular responses. This study investigates the role of PLD-mediated PA and DG formation in inducing phospholipase A2 (PLA2) activity in intact human neutrophils (PMNs) and in PMNs permeabilized with Staphylococcus aureusα-toxin. PMNs were labelled with [3H]arachidonic acid (AA) to assess AA release and metabolism and diacylglycerol formation, or with [3H]1-O-hexadecyl-2-lyso-glycerophosphatidylcholine for the determination of platelet-activating factor (PAF), PA and alkylacylglycerol production. In intact PMNs primed with tumour necrosis factor α before stimulation with N-formyl-Met-Leu-Phe, AA release and metabolism and PAF formation increased in parallel with enhanced PA and DG formation, and inhibition of PA and DG production led to a decrease in both AA release and PAF accumulation. In α-toxin-permeabilized PMNs, AA release and PAF production result from the specific activation of cytosolic PLA2 (cPLA2). In this system, PA and DG formation were always present when cPLA2 activation occurred; blocking PA and DG production inhibited AA release and PAF accumulation. Adding either PA or DG back to permeabilized cells (with endogenous PA and DG formation blocked) led to a partial restoration of AA release and PAF formation; a combination of PA and DGs reconstituted full cPLA2 activity. These results strongly suggest that products of PLD participate in activating cPLA2 in PMNs.

scholarly journals Interactions between Cytosolic Phospholipase A2 Activation and Mitochondrial Reactive Oxygen Species Production in the Development of Ventilator-Induced Diaphragm Dysfunction

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xian-Long Zhou ◽  
Xiao-Jun Wei ◽  
Shao-Ping Li ◽  
Rui-Ning Liu ◽  
Ming-Xia Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Phospholipase A2 ◽  
Cytosolic Phospholipase A2 ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Diaphragm Dysfunction ◽  
Cytosolic Phospholipase ◽  
Mitochondrial Ros ◽  
Cpla2 Activation

Cytosolic phospholipase A2 (cPLA2) has been reported to be critical for infection-induced mitochondrial reactive oxygen species (ROS) production and diaphragm dysfunction (DD). In the present study, we aim to investigate whether cPLA2 was involved in ventilator-induced diaphragm dysfunction (VIDD). Our results showed that mechanical ventilation (MV) induced cPLA2 activation in the diaphragm with excessive mitochondrial ROS generation and muscle weakness. Specific inhibition of cPLA2 with CDIBA resulted in decreased mitochondrial ROS levels and improved diaphragm forces. In addition, mitochondria-targeted antioxidant MitoTEMPO attenuated ventilator-induced mitochondrial oxidative stress and downregulated cPLA2 activation in vivo. Both CDIBA and MitoTEMPO were able to attenuate protein degradation, muscle atrophy, and weakness following prolonged MV. Furthermore, laser Doppler imaging showed that MV decreased diaphragm tissue perfusion and induced subsequent hypoxia. An in vitro study also demonstrated a positive association between cPLA2 activation and mitochondrial ROS generation in C2C12 cells cultured under hypoxic condition. Collectively, our study showed that cPLA2 activation positively interacts with mitochondrial ROS generation in the development of VIDD, and ventilator-induced diaphragm hypoxia serves as a possible contributor to this positive feedback loop.

The role of cytosolic phospholipase A2 in gastric damage induced by helicobacter pylori infection: in vivo and in vitro studies

2000 ◽  
Vol 118 (4) ◽  
pp. A732-A733
Author(s):  
Gerardo Nardone ◽  
Eileen Holicky ◽  
Jim R. Uhl ◽  
Vittorio Colantuoni ◽  
Lina Sabatino ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Phospholipase A2 ◽  
Cytosolic Phospholipase A2 ◽  
In Vitro Studies ◽  
Helicobacter Pylori Infection ◽  
Gastric Damage ◽  
Cytosolic Phospholipase

Role of phosphatidylinositol 4,5-bisphosphate in the activation of cytosolic phospholipase A2-α

2006 ◽  
Vol 81 (3-4) ◽  
pp. 113-125 ◽  
Author(s):  
Ludmilla Le Berre ◽  
Tomoko Takano ◽  
Joan Papillon ◽  
Serge Lemay ◽  
Andrey V. Cybulsky
Keyword(s):  
Phospholipase A2 ◽  
Cytosolic Phospholipase A2 ◽  
Cytosolic Phospholipase

scholarly journals An Essential Role of the Jak-2/STAT-3/Cytosolic Phospholipase A2Axis in Platelet-derived Growth Factor BB-induced Vascular Smooth Muscle Cell Motility

2004 ◽  
Vol 279 (44) ◽  
pp. 46122-46128 ◽  
Author(s):  
Indira Neeli ◽  
Zhimin Liu ◽  
Nagadhara Dronadula ◽  
Z. Alex Ma ◽  
Gadiparthi N. Rao
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Dominant Negative ◽  
Platelet Derived Growth Factor ◽  
Dominant Negative Mutant ◽  
Dependent Manner ◽  
Cytosolic Phospholipase ◽  
Negative Mutant

Platelet-derived growth factor-BB (PDGF-BB) is a potent motogen for vascular smooth muscle cells (VSMCs). To understand its motogenic signaling events, we have studied the role of the Janus-activated kinase/signal transducers and activators of transcription (Jak/STAT) pathway and cytosolic phospholipase A2(cPLA2). PDGF-BB stimulated tyrosine phosphorylation of Jak-2 and STAT-3 in a time-dependent manner in VSMCs. In addition, AG490 and Jak-2KEpRK5, a selective pharmacological inhibitor and a dominant negative mutant, respectively, of Jak-2, attenuated PDGF-BB-induced STAT-3 tyrosine phosphorylation and its DNA binding and reporter gene activities. PDGF-BB induced VSMC motility in a dose-dependent manner with a maximum effect at 10 ng/ml. Dominant negative mutant-dependent suppression of Jak-2 and STAT-3 blocked PDGF-BB-induced VSMC motility. PDGF-BB induced the expression of cPLA2in a Jak-2/STAT-3-dependent manner, and pharmacological inhibitors of cPLA2prevented PDGFBB-induced VSMC motility. Furthermore, either exogenous addition of arachidonic acid or forced expression of cPLA2rescued PDGF-BB-induced VSMC motility from inhibition by blockade of Jak-2 and STAT-3 activation. Together, these results for the first time show that PDGF-BB-induced VSMC motility requires activation of the Jak-2/STAT-3/cPLA2signaling axis.

Sign in / Sign up

Export Citation Format

Share Document