Induction of apoptosis in luteinized granulosa cells by the MAP kinase kinase (MEK) inhibitor PD98059.
Our objective is to test the hypothesis that inhibition of mitogen-activated protein (MAP) kinase kinase (MEK) with PD98059 in human luteinized granulosa cells will block epidermal growth (EGF)-stimulated MAP kinase activity and induce apoptosis. Luteinized granulosa cells from human in vitro fertilization aspirates were cultured and treated with the following: (1) vehicle; (2) PD98059; (3) EGF; (4) PD98059 + EGF. Treatment with PD98059 suppressed MAP kinase activity, inhibited MAP kinase phosphorylation by Western blot analysis, blocked nuclear translocation of phosphorylated MAP kinase by confocal microscopy, and increased percentages of subdiploid apoptotic nuclei by flow cytometry. Our data are the first evidence that a relationship may exist between the MAP kinase pathway and control of apoptosis in human luteinized granulosa cells. These results support the hypothesis that suppression of the MAP kinase pathway may lead to apoptosis in these cells.
Oliver
R H
RH
Department of Obstetrics, Gynecology and Women's Health, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Khan
S M
SM
Leung
B S
BS
Yeh
J
J
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors
D004791:Enzyme Inhibitors; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D004815:Epidermal Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one