Apoptosis induced clustering of IP(3)R1 in nuclei of non-differentiated PC12 cells

Karol Ondrias1, Lubomira Lencesova, Marta Sirova

  • 1Institute of Molecular Physiology and Genetics, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.

Insights

Inositol 1,4,5-trisphosphate (IP(3)) receptors are crucial in apoptosis. Their increased levels and nuclear translocation in non-differentiated cells suggest a role in regulating cell death via calcium signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Apoptosis Research

Background:

  • Inositol 1,4,5-trisphosphate (IP(3)) receptors are implicated in apoptosis regulation.
  • Their role in differentiated versus non-differentiated cells requires further elucidation.

Purpose of the Study:

  • To investigate the role of IP(3) receptors in apoptosis induction in PC12 cells.
  • To examine the changes in IP(3) receptor expression and localization during apoptosis.

Main Methods:

  • Apoptosis induction in PC12 cells using an apoptosis inducer set (AIK).
  • Measurement of IP(3) receptor mRNA and protein levels.
  • Inhibition of IP(3) receptor function using 2-APB and xestospongin.
  • Analysis of Bax and caspase-3 mRNA expression.
  • Microscopic examination of IP(3) receptor localization.

Main Results:

  • Apoptosis induction increased type 1 IP(3) receptor mRNA and protein in non-differentiated (ND) PC12 cells, but not in differentiated (D) cells.
  • IP(3) receptor inhibitors prevented apoptosis-induced increases in Bax and caspase-3.
  • Apoptosis led to IP(3) receptor clustering in the nucleus.
  • Intranuclear calcium levels decreased post-apoptosis induction.

Conclusions:

  • Type 1 IP(3) receptors are critical for apoptosis in ND PC12 cells.
  • Nuclear translocation of IP(3) receptors may enhance calcium permeability, contributing to apoptosis.
  • Changes in IP(3) receptor expression and localization are key events in apoptosis.

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