Related Experiment Video

Updated: Aug 21, 2026

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
07:13

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Published on: May 24, 2024

Proteinase-activated receptor 1 (PAR-1) and cell apoptosis

A N Flynn1, A G Buret

  • 1Department of Biological Sciences and Mucosal Inflammation Research Group, The University of Calgary, Calgary, Alberta T2N 1N4, Canada.

Apoptosis : an International Journal on Programmed Cell Death
|October 27, 2004
PubMed

Insights

Proteinase-activated receptor 1 (PAR-1) influences programmed cell death (apoptosis) in various cells, with effects varying by agonist dosage. This receptor

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Proteinase-activated receptor 1 (PAR-1) is a G protein-coupled receptor activated by serine proteases.
  • PAR-1 plays roles in diverse physiological processes, including inflammation, thrombosis, and cell survival.
  • Its role in programmed cell death (apoptosis) is complex and context-dependent.

Purpose of the Study:

  • To review the multifaceted roles of PAR-1 in modulating programmed cell death (apoptosis).
  • To explore the signaling pathways and cellular targets involved in PAR-1-mediated apoptosis.
  • To discuss the implications of PAR-1 activation in infectious diseases.

Main Methods:

  • Literature review of studies investigating PAR-1 and apoptosis.
  • Analysis of signaling pathways (e.g., JAK/STAT, RhoA, ERK1/2, Bcl-2 family) modulated by PAR-1.
  • Examination of cellular responses in neuronal, endothelial, epithelial, fibroblast, and tumor cells.

Main Results:

  • PAR-1 activation can either induce or inhibit apoptosis, contingent on agonist concentration (thrombin or synthetic activators).
  • PAR-1 affects apoptosis in a wide range of cell types, including critical roles in neuronal and endothelial cells.
  • Diverse intracellular signaling cascades mediate PAR-1's opposing effects on cell death.

Conclusions:

  • PAR-1 is a key regulator of apoptosis with context-dependent outcomes.
  • Understanding PAR-1 signaling is crucial for therapeutic strategies targeting cell death.
  • PAR-1 activation may contribute to the pathogenesis of infectious diseases via microbial proteases.

More Related Videos

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

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

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 cells.
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...
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...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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.