Protein serine/threonine phosphatase 2A activity is inhibited by cAMP in MA-10 cells.
PP1 and PP2A are members of the protein serine/threonine phosphatases (PPs) family and their activities have been proposed as a requirement for hormone- and cAMP-regulated steroid synthesis. These findings raise the question whether the PPs activity is increased by hormonal action in steroidogenic systems. Thus, the aim of the study was to evaluate the action of cAMP on the activity of PP1 and PP2A in MA-10 Leydig cells. Our results demonstrate that 8Br-cAMP stimulation produces a transient inhibition of PP2A activity. In contrast, PP1 activity remains unchangeable. As reported in other steroidogenic cells, cAMP-induced steroidogenesis in MA-10 cells is reduced by Cantharidin (Can) and also by Calyculin A (CA), two chemically unrelated PP1/PP2A inhibitors (data not shown). Taking into account the inhibitory effect of cAMP treatment on PP2A activity, the latest findings result paradoxical. Therefore, we next evaluated the action of these compounds on total protein synthesis. Can 10(-5) M and CA 10(-7) M markedly reduced total protein synthesis (35 and 50% respectively) in MA-10 cells, measured by 35S-methonine incorporation. These results suggest that hormone-dependent steroidogenesis is working through inhibition of PP2A-dependent dephosphorylation and the effect of PP1/PP2A inhibitors on steroidogenesis may be due to a general inhibition of protein synthesis rather than to a specific action on StAR protein induction.
Poderoso
Cecilia
C
Department of Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Paz
Cristina
C
Gorostizaga
Alejandra
A
Cornejo Maciel
Fabiana
F
Mendez
Carlos F
CF
Podesta
Ernesto J
EJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002193:Cantharidin / Q000008:administration & dosage; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008387:Marine Toxins; D008715:Methionine / Q000378:metabolism; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014176:Protein Biosynthesis; D054648:Protein Phosphatase 2
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D010080:Oxazoles; D015124:8-Bromo Cyclic Adenosine Monophosphate; C059041:calyculin A; D008715:Methionine; D000242:Cyclic AMP; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D002193:Cantharidin