Evidence for macromolecular crowding as a direct apoptotic stimulus
Priyanka S Rana1, Manabu Kurokawa1, Michael A Model2
1Department of Biological Sciences, Kent State University, Kent, OH 44242, USA.
Journal of Cell Science
|May 13, 2020
Summary
Cell shrinkage, not just ion loss, can trigger apoptosis. This process is influenced by macromolecular crowding, impacting caspase activation and cytochrome c release.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis (programmed cell death) has been linked to potassium loss and cell shrinkage, but their precise roles are debated.
- Understanding the interplay between cellular volume and apoptotic pathways is crucial for cell death research.
Purpose of the Study:
- To investigate the relationship between cell volume changes and apoptosis.
- To determine if cell shrinkage or ion loss is the primary driver of apoptosis.
- To explore the role of macromolecular crowding in apoptotic signaling.
Main Methods:
- Utilized ionophores to manipulate intracellular sodium and potassium levels in HeLa and MDCK cells.
- Induced cell swelling and subsequent shrinkage using sucrose.
- Administered staurosporine (a protein kinase inhibitor) to induce apoptosis under varying cell volume conditions.
- Assessed apoptotic features including phosphatidylserine inversion, caspase activation, and cytochrome c release.
Main Results:
- Cell shrinkage, independent of intracellular ion composition or actin cytoskeleton status, can induce apoptosis.
- Swollen cells remained viable, indicating shrinkage is the trigger.
- Shrinkage-induced apoptosis exhibited classical features like caspase activation and cytochrome c release.
- Potassium dependence of caspase activation was observed only in swollen cells with reduced cytosolic protein density.
Conclusions:
- Persistent cell shrinkage is a potent inducer of intrinsic apoptosis.
- Macromolecular crowding, particularly in swollen cells, significantly influences caspase activation and the apoptotic pathway.
- Cell volume regulation plays a critical role in determining the cell's fate towards apoptosis.
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