Related Experiment Video

Updated: Mar 28, 2026

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

9.2K

Glycogen Synthase Kinase-3β and Caspase-2 Mediate Ceramide- and Etoposide-Induced Apoptosis by Regulating the

Chiou-Feng Lin1,2, Cheng-Chieh Tsai3, Wei-Ching Huang4

  • 1Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.

Plos One
|January 5, 2016
PubMed

Insights

Glycogen synthase kinase-3β (GSK-3β) and caspase-2 regulate apoptosis by affecting Mcl-1 and lysosomal membrane permeabilization. This study reveals their role in the lysosomal-mitochondrial apoptosis pathway.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Glycogen synthase kinase-3β (GSK-3β) is implicated in apoptosis.
  • Caspase cascades, including caspase-2 and caspase-8, are critical in programmed cell death.
  • Mitochondrial apoptosis and lysosomal membrane permeabilization (LMP) are key apoptotic pathways.

Purpose of the Study:

  • To elucidate the roles of GSK-3β and caspase-2 in apoptosis induction.
  • To investigate the regulation of Mcl-1 destabilization and cathepsin D-mediated caspase-8 activation.
  • To understand the involvement of the lysosomal-mitochondrial pathway in apoptosis.

Main Methods:

  • Induction of apoptosis using C2-ceramide or etoposide.
  • Assessment of lysosomal membrane permeabilization (LMP) and mitochondrial transmembrane potential.
  • Analysis of cathepsin D translocation, Mcl-1 expression, and caspase activation.
  • Inhibition studies using GSK-3β and caspase-2 inhibitors.

Main Results:

  • Ceramide or etoposide treatment induced LMP, mitochondrial dysfunction, and apoptosis.
  • Cathepsin D translocation to the cytoplasm following LMP was essential for apoptosis.
  • GSK-3β and caspase-2 inhibition prevented Mcl-1 destabilization, LMP, and apoptosis.
  • Mcl-1 localized to lysosomes and its overexpression inhibited lysosomal-mitochondrial apoptosis.

Conclusions:

  • GSK-3β and caspase-2 are crucial regulators of apoptosis.
  • Mcl-1 destabilization and lysosomal membrane permeabilization are key events in this pathway.
  • The study highlights the GSK-3β/caspase-2/Mcl-1 axis in the lysosomal-mitochondrial apoptotic signaling.

More Related Videos

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.5K
Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

5.8K

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.5K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.2K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
16.9K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
5.0K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
11.1K