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Neddylation inactivation affects cell cycle and apoptosis in sheep follicular granulosa cells

Xiaowei Qin1, Wenqing Dang1, Xiaofeng Yang1

  • 1Animal Genetics, Breeding and Reproduction Laboratory, College of Animal Science, Shanxi Agricultural University, Taigu, Shanxi, China.

Journal of Cellular Physiology
|May 17, 2022
PubMed

Insights

Protein neddylation inactivation inhibits sheep follicular granulosa cell proliferation and induces apoptosis. This study reveals neddylation

Area of Science:

  • Reproductive biology
  • Molecular oncology
  • Cellular metabolism

Background:

  • Neddylation is crucial for protein regulation, but its role in sheep follicular granulosa cells (GCs) is understudied.
  • Understanding neddylation mechanisms in GCs is vital for reproductive health and cancer research.

Purpose of the Study:

  • To investigate the mechanism of neddylation in regulating sheep follicular GCs proliferation and apoptosis.
  • To explore the impact of neddylation inactivation on key cellular pathways and mitochondrial function in GCs.

Main Methods:

  • Sheep follicular GCs were treated with MLN4924, a specific neddylation inhibitor.
  • Cell proliferation, apoptosis, cell cycle, protein expression, signaling pathways (Akt, JAK2/STAT3, FOXO), and mitochondrial functions were analyzed.

Main Results:

  • MLN4924 significantly attenuated GC proliferation and induced apoptosis by upregulating NOXA and downregulating Bcl-2/MCL-1.
  • Neddylation inactivation led to Wee1 and c-Myc accumulation, causing G2/M-phase arrest.
  • MLN4924 altered Akt, JAK2/STAT3, and FOXO signaling pathways, promoted GC glycolysis, increased ROS production, and disrupted mitochondrial morphology.

Conclusions:

  • Neddylation plays a critical, previously unrecognized role in regulating sheep follicular GCs proliferation.
  • Targeting neddylation may offer a novel therapeutic strategy for gynecological cancers and reproductive disorders.
Keywords:
MLN4924apoptosiscell cyclegranulosa cellsneddylation

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