Mitochondria play a role in the development of non-apoptotic programmed cell death of neutrophils induced by ONO-AE-248.
We previously reported that ONO-AE-248, a selective EP3 receptor agonist, has been shown to cause neutrophil death without the typical features of apoptosis and necrosis. However, the mechanism of the neutrophil death is unclear. By using Western blotting, flow cytometry (FACS) and confocal laser scanning microscopy (CLSM), we investigated the cellular signal transduction pathways of the neutrophil death. The research results showed that the neutrophil death induced by ONO-AE-248 did not show the morphologic changes of apoptosis and was not associated with the activity of caspase-3, caspase-8, and phosphorylation of p38-MAPK. However, impairment of mitochondria transmembrane potential has been found during the process of cell death. These findings suggested that ONO-AE-248 induced a non-apoptotic programmed cell death of neutrophils through partially mitochondria signaling transduction pathway.
Liu
Jiajia
J
Laboratory of Molecular Biology, Department of Immunology, Luzhou Medical College, Luzhou, Sichuan 646000, China. jiajialiu08@hotmail.com
He
Hao
H
Zhang
Zi
Z
Jiang
Shixu
S
Akahoshi
Tohru
T
Yang
Jian
J
Li
Juan
J
He
Tao
T
D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000276:immunology; D018613:Microscopy, Confocal / Q000379:methods; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D018078:Receptors, Prostaglandin E / Q000819:agonists; D058308:Receptors, Prostaglandin E, EP3 Subtype; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C121546:ONO AE 248; C545647:PTGER3 protein, human; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053181:Caspase 8; D015232:Dinoprostone