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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
06:26

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but also anti-apoptotic calcium-dependent

Arnaud Berthier1, Stéphanie Lemaire-Ewing, Céline Prunet

  • 1INSERM U498--Métabolisme des lipoprotéines et interactions vasculaires, Dijon Cedex, France.

The FEBS Journal
|June 16, 2005
PubMed

Insights

7-ketocholesterol triggers apoptosis in atherosclerosis via calcium-dependent pathways. This study reveals complex mechanisms involving both pro-apoptotic and survival pathways, highlighting 7-ketocholesterol

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathophysiology

Background:

  • Oxysterols, especially 7-ketocholesterol, are implicated in atherosclerosis.
  • 7-ketocholesterol is suspected to induce apoptosis in vascular cells and macrophages.
  • Previous research linked 7-ketocholesterol-induced apoptosis to increased cytosolic Ca2+ and the mitochondrial pathway via calcineurin and BAD.

Purpose of the Study:

  • To investigate other calcium-dependent pathways involved in 7-ketocholesterol-induced cytotoxicity.
  • To elucidate the roles of the MEK-->ERK pathway and the BH3-only protein Bim in this process.

Main Methods:

  • Utilized human monocytic THP-1 cells.
  • Administered 7-ketocholesterol treatment.
  • Employed the MEK inhibitor U0126.
  • Analyzed protein interactions and cellular pathways.

Main Results:

  • Demonstrated calcium-dependent activation of the MEK-->ERK survival pathway by tyrosine kinase PYK 2, delaying apoptosis.
  • Showed 7-ketocholesterol induces release of Bim-LC8 from microtubule-associated dynein and association with Bcl-2.
  • Identified involvement of Bim in 7-ketocholesterol-induced apoptosis.

Conclusions:

  • 7-ketocholesterol-induced apoptosis is a complex, multifactorial process.
  • Multiple calcium-dependent pro-apoptotic pathways are activated.
  • A calcium-dependent survival pathway (MEK-->ERK) also plays a role, modulating the apoptotic response.

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