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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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

Published on: December 27, 2016

Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway

Xiao-Ming Ou1, Kevin Chen, Jean C Shih

  • 1Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 11, 2006
PubMed

Insights

Monoamine oxidase A (MAO A) and transcription factor R1 regulate cell death and proliferation. Inhibiting MAO A prevents apoptosis, while R1

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Monoamine oxidase A (MAO A) degrades neurotransmitters and produces reactive oxygen species, potentially causing neuronal cell death.
  • Transcription factor R1 (RAM2/CDCA7L/JPO2) has been identified as an inhibitor of MAO A promoter and enzymatic activity.
  • The roles of MAO A and R1 in cellular apoptosis and proliferation signaling pathways require further elucidation.

Purpose of the Study:

  • To investigate the involvement of MAO A and R1 in serum starvation-induced apoptosis.
  • To explore the relationship between MAO A, R1, and key apoptotic regulators such as p38 kinase, Bcl-2, and caspase-3.
  • To determine the function of MAO A and R1 in the c-Myc-induced proliferative signaling pathway.

Main Methods:

  • Utilized serum starvation models to induce apoptosis in cells.
  • Employed MAO A inhibitors, p38 kinase inhibitors, and R1 overexpression/small interfering RNA (siRNA) techniques.
  • Conducted immunoprecipitation and immunohistochemistry experiments to assess protein interactions and localization.
  • Compared apoptosis levels in cortical brain cells from MAO A-deficient mice and wild-type (WT) controls.

Main Results:

  • Serum starvation increased p38 kinase, MAO A, and caspase-3, while decreasing Bcl-2 and R1.
  • MAO A and R1 were found to be downstream of p38 kinase and Bcl-2, but upstream of caspase-3.
  • Inhibition of MAO A significantly reduced apoptosis, and this effect was corroborated in MAO A-deficient mice.
  • MAO A and R1 were identified as crucial components in the c-Myc-induced proliferation pathway, acting upstream of cyclin D1 and E2F1.

Conclusions:

  • MAO A inhibition effectively prevents apoptosis, highlighting its pro-apoptotic role.
  • R1 acts as a repressor of MAO A, influencing both apoptotic and proliferative signaling.
  • The study elucidates the intricate roles of MAO A and R1 in regulating cell fate decisions, offering potential therapeutic targets.

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