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ZFIN ID: ZDB-PUB-171213-1
Relative importance of phosphatidylinositol-3 kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK3/1) signaling during maturational steroid-induced meiotic G2-M1 transition in zebrafish oocytes
Das, D., Nath, P., Pal, S., Hajra, S., Ghosh, P., Maitra, S.
Date: 2017
Source: Zygote (Cambridge, England)   26(1): 62-75 (Journal)
Registered Authors:
Keywords: GVBD, Meiosis, Oocyte, PKA, Zebrafish
MeSH Terms:
  • Animals
  • Cyclic AMP/metabolism
  • Enzyme Inhibitors/pharmacology
  • Female
  • G2 Phase/physiology
  • In Vitro Oocyte Maturation Techniques
  • MAP Kinase Kinase 1/metabolism
  • Meiosis/physiology
  • Mitogen-Activated Protein Kinase 1/antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1/metabolism*
  • Mitogen-Activated Protein Kinase 3/antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3/metabolism*
  • Oocytes/physiology*
  • Phosphatidylinositol 3-Kinases/antagonists & inhibitors
  • Phosphatidylinositol 3-Kinases/metabolism*
  • Phosphorylation
  • Pregnenes/pharmacology
  • Proto-Oncogene Proteins c-akt/metabolism*
  • Signal Transduction/drug effects
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 29229010 Full text @ Zygote
Participation and relative importance of phosphatidylinositol-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling, either alone or in combination, have been investigated during 17α,20β-dihydroxy-4-pregnen-3-one (DHP)-induced meiotic G2-M1 transition in denuded zebrafish oocyte. Results demonstrate that concomitant with rapid phosphorylation (activation) of Akt (Ser473) and MAPK (ERK1/2) at as early as 15 min of incubation, DHP stimulation promotes enhanced an GVBD response and histone H1 kinase activation between 1 and 5 h in full-grown oocytes in vitro. While p-Akt reaches its peak at 60 to 90 min and undergoes downregulation to the basal level by 240 min, ERK1/2 phosphorylation (activation) increases gradually until 120 min and remains high thereafter. Although, priming with MEK1/2 inhibitor U0126 is without effect, PI3K inhibitors, wortmannin or LY294002, delay the GVBD response significantly (P < 0.001) until 3 h but not at 5 h of incubation. Interestingly, blocking PI3K and MEK function together could abrogate steroid-induced oocyte maturation at all time points tested. While DHP stimulation promotes phospho-PKA catalytic (p-PKAc) dephosphorylation (inactivation) between 30-120 min of incubation, simultaneous inhibition of PI3K and MEK1/2 kinases abrogates DHP action. Conversely, elevated intra-oocyte cAMP, through priming with either adenylyl cyclase (AC) activator forskolin (FK) or dibutyryl cAMP (db-cAMP), abrogates steroid-induced Akt and ERK1/2 phosphorylation. Taken together, these results suggest that DHP-induced Akt and ERK activation precedes the onset of meiosis (GVBD response) in a cAMP-sensitive manner and PI3K/Akt and MEK/MAPK pathways together have a pivotal influence in the downregulation of PKA and resumption of meiotic maturation in zebrafish oocytes in vitro.