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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

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Comparative proteomic analysis of cell cycle-dependent apoptosis induced by transforming growth factor-beta

Hong-Yu Tian1, Ke-Hua Zhang, Xia Gao

  • 1Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Biochimica Et Biophysica Acta
|May 20, 2009
PubMed

Insights

Transforming growth factor-beta (TGF-beta) triggers cell death in G2/M phase hepatocytes by downregulating glutamine synthetase. This mechanism explains TGF-beta

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Hepatology

Background:

  • Transforming growth factor-beta (TGF-beta) exhibits dual roles in hepatocytes, inducing apoptosis and epithelial-mesenchymal transition (EMT).
  • The precise molecular mechanisms underlying TGF-beta's cell cycle-dependent effects on apoptosis and EMT remain largely unelucidated.

Purpose of the Study:

  • To investigate the proteomic alterations in hepatocytes following TGF-beta treatment.
  • To elucidate the role of glutamine synthetase in TGF-beta-induced apoptosis and EMT.
  • To understand the cell cycle-dependent mechanisms of TGF-beta's biological effects.

Main Methods:

  • Two-dimensional gel electrophoresis (2D-PAGE) for global proteome analysis.
  • MALDI-TOF/TOF mass spectrometry for protein identification.
  • Immunoblotting to confirm protein expression changes.
  • Cell synchronization in G2/M or G1/S phases.
  • Treatment with TGF-beta and exogenous glutamine.

Main Results:

  • TGF-beta significantly altered the expression of 44 proteins in G2/M phase-synchronized hepatocytes.
  • TGF-beta induced a specific downregulation of glutamine synthetase in G2/M phase cells.
  • Exogenous glutamine abolished TGF-beta-induced apoptosis in G2/M and non-synchronized cells but not EMT.

Conclusions:

  • Glutamine synthetase downregulation is implicated in TGF-beta-induced G2/M phase-dependent apoptosis.
  • TGF-beta exerts multifunctional effects on hepatocytes, differentially regulating apoptosis and EMT.
  • These findings offer novel insights into the complex mechanisms of TGF-beta signaling.

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