Related Experiment Video

Updated: Aug 14, 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

A ligand-receptor pair that triggers a non-apoptotic form of programmed cell death

S Castro-Obregón1, G Del Rio, S F Chen

  • 1Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.

Cell Death and Differentiation
|July 11, 2002
PubMed

Insights

Researchers discovered substance P and its receptor, neurokinin-1 receptor (NK(1)R), trigger a novel form of programmed cell death. This non-apoptotic cell death pathway is distinct from apoptosis and offers new research avenues.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis is a crucial form of programmed cell death mediated by various receptors like Fas.
  • Understanding apoptosis signal transduction pathways is vital for biological research.
  • The neuropeptide substance P and its receptor, neurokinin-1 receptor (NK(1)R), are widely involved in the central and peripheral nervous systems, particularly in pain and depression.

Purpose of the Study:

  • To identify and characterize a novel ligand-receptor pair mediating programmed cell death.
  • To investigate if substance P and neurokinin-1 receptor (NK(1)R) can induce cell death independent of apoptosis.
  • To explore the characteristics and signaling pathways of this alternative cell death mechanism.

Main Methods:

  • Investigated the effect of substance P on neuronal cell death in hippocampal, striatal, and cortical neurons.
  • Utilized NK(1)R-transfected human embryonic kidney cells to confirm the receptor's role.
  • Analyzed cell death morphology, gene expression requirements, and caspase activation.
  • Characterized the signal transduction pathway activated by the substance P-NK(1)R interaction.

Main Results:

  • Substance P induces a form of programmed cell death in neurons that is morphologically distinct from apoptosis.
  • This cell death is gene expression-dependent but caspase activation-independent.
  • The substance P-induced cell death was replicated in NK(1)R-transfected cells, confirming the receptor's role.
  • Identified a novel death pathway activated by the neurokinin-1 receptor.

Conclusions:

  • The substance P-neurokinin-1 receptor (NK(1)R) pair mediates a non-apoptotic form of programmed cell death.
  • This discovery reveals a distinct cell death pathway separate from classical apoptosis.
  • Provides a new system for studying non-apoptotic cell death mechanisms and their associated signal transduction.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

Related Concept Videos

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 20th century...
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 reduction of the tissue.
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...
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...
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 pro-apoptotic...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...