Identification and Characterization of a Novel LPA2 Receptor Agonist: Antiapoptotic and Radiomitigative Properties of GRI977143 a Novel Nonlipid LPA2 Receptor Agonist - Couverture souple

Nagyne Kiss, Gyongyi; Tigyi, Gabor

 
9783330713376: Identification and Characterization of a Novel LPA2 Receptor Agonist: Antiapoptotic and Radiomitigative Properties of GRI977143 a Novel Nonlipid LPA2 Receptor Agonist
Couverture souple
ISBN 10 : 3330713372 ISBN 13 : 9783330713376
Editeur : GlobeEdit, 2016

Synopsis

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 γ-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-α, and γ-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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Présentation de l'éditeur

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 γ-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-α, and γ-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.

Biographie de l'auteur

Gyongyi Nagyne Kiss M.D., Ph.D. is assistant professor at the Department of Biochemistry and Medical Chemistry, University of Pécs, Medical School, Pécs, Hungary. Gabor Tigyi M.D., Ph.D is Harriet Van Vleet Professor and department chair at the Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.

Les informations fournies dans la section « A propos du livre » peuvent faire référence à une autre édition de ce titre.

Éditeur
GlobeEdit
Date d'édition
2016
Langue
anglais
ISBN 10 
3330713372
ISBN 13 
9783330713376
Reliure
Broché
Nombre de pages
120
Coordonnées du fabricant
non disponible
Personne responsable
non disponible