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Identification and Characterization of a Novel LPA2 Receptor Agonist

Identification and Characterization of a Novel LPA2 Receptor Agonistvon Gyongyi Nagyne Kiss Sie sparen 16% des UVP sparen 16%
Über Identification and Characterization of a Novel LPA2 Receptor Agonist

The endogenous lipid mediator lysophosphatidic acid (LPA) regulates fundamental cellular responses, ranging from survival through proliferation to motility and migration. Acting through one of its cell membrane receptors, the LPA2 receptor, LPA protects against chemotherapy- and ¿-irradiation-induced apoptosis. Virtual screening led to the identification of GRI977143 (GRI), a novel nonlipid LPA2 receptor agonist. GRI reduced activation of caspases 3, 7, 8, and 9, and inhibited Bax translocation, poly (ADP-ribose) polymerase 1 cleavage, and DNA fragmentation in the serum withdrawal, Adriamycin, TNF-¿, and ¿-irradiation apoptosis models. GRI acted as a radiomitigator and rescued the lives of mice when administered 24 h after lethal radiation exposure. GRI also inhibited bystander apoptosis elicited by proapoptotic mediators produced by irradiated cells. Prosurvival and radiomitigative effect of GRI may in part be attributed to the LPA2 receptor-mediated activation of the extracellular signal regulated kinases 1 and 2. GRI represents an excellent candidate for further development of radiomitigative drugs, and agents that prevent apoptosis in degenerative and inflammatory diseases.

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  • Sprache:
  • Englisch
  • ISBN:
  • 9783330713376
  • Einband:
  • Taschenbuch
  • Seitenzahl:
  • 120
  • Veröffentlicht:
  • 19. Dezember 2016
  • Abmessungen:
  • 150x8x220 mm.
  • Gewicht:
  • 197 g.
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Verlängerte Rückgabefrist bis 31. Januar 2025

Beschreibung von Identification and Characterization of a Novel LPA2 Receptor Agonist

The endogenous lipid mediator lysophosphatidic acid (LPA) regulates fundamental cellular responses, ranging from survival through proliferation to motility and migration. Acting through one of its cell membrane receptors, the LPA2 receptor, LPA protects against chemotherapy- and ¿-irradiation-induced apoptosis. Virtual screening led to the identification of GRI977143 (GRI), a novel nonlipid LPA2 receptor agonist. GRI reduced activation of caspases 3, 7, 8, and 9, and inhibited Bax translocation, poly (ADP-ribose) polymerase 1 cleavage, and DNA fragmentation in the serum withdrawal, Adriamycin, TNF-¿, and ¿-irradiation apoptosis models. GRI acted as a radiomitigator and rescued the lives of mice when administered 24 h after lethal radiation exposure. GRI also inhibited bystander apoptosis elicited by proapoptotic mediators produced by irradiated cells. Prosurvival and radiomitigative effect of GRI may in part be attributed to the LPA2 receptor-mediated activation of the extracellular signal regulated kinases 1 and 2. GRI represents an excellent candidate for further development of radiomitigative drugs, and agents that prevent apoptosis in degenerative and inflammatory diseases.

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