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The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.

ڈونالڈ ٹرمپ کی صلاح کے بعد نیویارک مں جراثیم کو مارنے والی اشیا کے پینے کے 30 سے یادہ معاملے سامنے آئے ہیں۔ شہر کے ہیلتھ ڈپارٹمینٹ کے تحت آنے والے (Poison Control Center) کے پاس اس طرح کے معاملات کی گزشتہ 18گھنٹوں میں 30 سے زیادہ کالس آئی ہیں۔ حالانکہ ان میں سے کسی بھی نہ ےو موت ہوئی ہ ہی کسی کو اسپتال(hospital admit) میں داخل کرنے کی ضرورت پڑی ہے۔ ان میں سے زیادہ تر معاملے گھر کی صاف۔صفائی کیلئے استعمال کئے جانے کیلئے استعمال کئے جانے والا (lizol) کے استعمال سے جڑے ہیں۔

کمپنی نے لوگوں سے کہا، " مہربانی کرکے انہیں نہ پئیں، یہ صحت کیلئے کافی خطرناک ہیں، ان سے موت بھی ہوسکتی ہے"۔ ریکٹ بینکسر (Reckitt Benckiser-RBGLY) نے کہا کہ امریکی صدر ڈونالڈ ٹرمپ کے بیان کے بعد سوشل میڈیا پر گمراہ کن خبروں کو پھیلایا جارہا ہے۔ یہ سبھی غلط ہے۔

Title: Don't Drink or Inject Our Product, Lysol Maker Says in Response to Trump Remark
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Apr 29, 2020

Joel Clement appeared on CNN's Erin Burnett OutFront on April 23, 2020.  In this blog post for the Union of Concerned Scientists, he elaborates on what he wishes he had said during that interview.

Wonder Land: The dispute between "proven" therapies to treat coronavirus and taking risks for people at death’s door. Images: Everett Collection/Getty Images Composite: Mark Kelly