Activation of PKC epsilon induces lactotroph proliferation through ERK1/2 in response to phorbol ester.
The aim of this investigation was to contribute to current knowledge about intracellular mechanisms that are involved in lactotroph cell proliferation, by evaluating the role of PKCalpha, PKCepsilon and extracellular-signal regulated kinase (ERK) 1/2 in response to phorbol 12-myristate13-acetate (PMA). In primary pituitary cultures, the activation of protein kinase C (PKC) by PMA for 15 min stimulated lactotroph proliferation; whereas a prolonged activation for 3-8h diminished this proliferative effect. The use of PMA for 15 min-activated PKCepsilon and ERK1/2, whereas incubation with PMA for 3 h induced PKCalpha activation and attenuated the PMA-triggered phosphorylation of ERK1/2. The following inhibitors: PKCs (bisindolylmaleimide I), PKCepsilon (epsilonV1 peptide) and ERK1/2 (PD98059) prevented the mitogenic activity induced by PMA for 15 min. Lactotroph cells stimulated with PMA for 15 min showed a translocation of PKCepsilon to membrane compartment and nucleus. These results thus establish that PKCepsilon plays an essential role in the lactotroph proliferation induced by PMA by triggering signals that involve ERK1/2 activation.
Petiti
Juan Pablo
JP
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Enrique Barros, 5000 Córdoba, Argentina. jpetiti@cmefcm.uncor.edu
De Paul
Ana Lucía
AL
Gutiérrez
Silvina
S
Palmeri
Claudia Mariela
CM
Mukdsi
Jorge Humberto
JH
Torres
Alicia Inés
AI
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D052682:Lactotrophs / Q000166:cytology* / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D051744:Protein Kinase C-epsilon; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate