The phenoxazine derivative Phx-1 suppresses IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells.
Antigen-induced aggregation of the high affinity IgE receptor (FcepsilonRI) on mast cells induces degranulation to release chemical mediators, leading to acute allergic inflammation. We have demonstrated that the treatment of rat mast cells, RBL-2H3, with a phenoxazine derivative Phx-1 (2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one) suppresses the antigen-induced degranulation. Biochemical analysis reveals that the complementary signaling pathway through Gab2 and Akt is inhibited by this compound in mast cells. These findings suggest that phenoxazine derivatives may have a therapeutic potential for allergic diseases by inhibiting mast cell degranulation.
Enoki
Eisuke
E
Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Japan.
Sada
Kiyonao
K
Qu
Xiujuan
X
Kyo
Shinkou
S
Miah
S M Shahjahan
SM
Hatani
Tomoko
T
Tomoda
Akio
A
Yamamura
Hirohei
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005544:Forecasting; D007073:Immunoglobulin E / Q000494:pharmacology* / Q000502:physiology; D015471:Leukemia, Basophilic, Acute / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology*; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017455:Receptors, IgE / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors / Q000378:metabolism
C104202:2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one; C470370:3-amino-1,4a-dihydro-4a,8-dimethyl-2H-phenoxazine-2-one; D048868:Adaptor Proteins, Signal Transducing; C490893:Gab2 protein, rat; D010078:Oxazines; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; D007073:Immunoglobulin E; D000001:Calcimycin; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D001619:beta-N-Acetylhexosaminidases