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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Micro-calpain regulates caspase-dependent and apoptosis inducing factor-mediated caspase-independent apoptotic

Lei Liu1, Da Xing, Wei R Chen

  • 1MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, South China Normal University, Guangzhou, China.

International Journal of Cancer
|August 26, 2009
PubMed

Insights

Micro-calpain activation is crucial for cisplatin-induced apoptosis in lung cancer cells. It regulates both caspase-dependent and apoptosis-inducing factor (AIF) release pathways, offering potential therapeutic targets.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Cisplatin is a key chemotherapy drug inducing apoptosis through caspase-dependent and -independent routes.
  • The exact regulatory mechanisms governing these apoptotic pathways remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of micro-calpain in cisplatin-induced apoptosis in human lung adenocarcinoma cells.
  • To determine if micro-calpain regulates both caspase-dependent and caspase-independent apoptotic pathways.

Main Methods:

  • Assessed calpain activation using fluorescent substrates post-cisplatin treatment.
  • Utilized confocal imaging to track apoptosis-inducing factor (AIF) release.
  • Investigated the effect of suppressing micro-calpain expression and using calpain inhibitors (calpeptin, PD150606) on cell death and caspase activity.

Main Results:

  • Micro-calpain activation occurred early, preceding AIF release and caspase activation.
  • Inhibition of micro-calpain significantly protected cells from death, reduced caspase activity, and blocked AIF redistribution.
  • Mitochondrial micro-calpain was shown to directly trigger AIF truncation and release, independent of caspases or cathepsins.

Conclusions:

  • Micro-calpain activation is essential for regulating both caspase-dependent and AIF-mediated caspase-independent apoptosis induced by cisplatin.
  • Micro-calpain represents a critical regulator and potential therapeutic target in cisplatin-induced apoptotic signaling.

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