Related Experiment Video
Updated: Jul 18, 2026
07:42
Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
The cytoprotective protein C pathway.
Laurent O Mosnier1, Berislav V Zlokovic, John H Griffin
1Department of Molecular and Experimental Medicine (MEM-180), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA.
Blood
|November 18, 2006
Summary
Activated protein C (APC) offers cytoprotective benefits beyond its anticoagulant role. Research shows APC stabilizes endothelial barriers and reduces inflammation, suggesting potential for treating sepsis, thrombosis, and stroke.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Protein C deficiency is linked to thrombosis and purpura fulminans.
- Activated protein C (APC) is known for its anticoagulant properties, inhibiting factors Va and VIIIa.
- APC demonstrated mortality reduction in severe sepsis patients (PROWESS trial).
Purpose of the Study:
- To review recent in vitro and in vivo studies on the direct cytoprotective effects of APC.
- To explore the molecular mechanisms and therapeutic potential of APC's cytoprotective actions.
- To differentiate structural features responsible for anticoagulant versus cytoprotective effects.
Main Methods:
- Literature review of in vitro and in vivo studies.
- Analysis of research on APC's interactions with its receptors (EPCR, PAR-1).
- Examination of studies detailing APC's effects on gene expression, inflammation, apoptosis, and endothelial barrier function.
Main Results:
- APC exhibits direct cytoprotective effects, including altered gene expression, anti-inflammatory actions, antiapoptosis, and endothelial barrier stabilization.
- APC's cytoprotection is mediated by its receptors: endothelial cell protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1).
- Distinct structural features mediate APC's anticoagulant and cytoprotective actions, suggesting potential for developing specialized variants.
Conclusions:
- APC possesses pleiotropic activities with potential therapeutic applications in sepsis, thrombosis, and ischemic stroke.
- Developing APC variants that enhance cytoprotective effects while minimizing anticoagulant activity and bleeding risk is a promising strategy.
- Further research into the molecular mechanisms of APC's cellular effects is warranted.
Related Concept Videos
01:17The 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...
01:31The 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...
01:13The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
02:18The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
01:27Complement System
The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
01:21Cytotoxic Edema: Pathophysiology
Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...