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"Dead Cells Talking": The Silent Form of Cell Death Is Not so Quiet.

Jäger R, Fearnhead HO - Biochem Res Int (2012)

Bottom Line: After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates.Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues.Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, 53359 Rheinbach, Germany.

ABSTRACT
After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.

No MeSH data available.


Related in: MedlinePlus

Apoptotic stimuli activate caspases, triggering the proteolysis of a large number of intracellular substrates. The cleavage of many of these, including iCAD and lamins, is necessary for the morphological and biochemical changes of apoptosis. Other substrates have as yet undefined roles, while the cleavage of iPLA2 is critical for the paracrine signalling that induces compensatory proliferation. Cleavage of iPLA2 increases its activity, so raising the levels of PGE2 and LPC. PGE2 in turn activates EP2 G protein-coupled receptors on stem or progenitor cells. Intracellular signalling downstream of EP2 activates β-catenin and leads to cell proliferation. LPC and ATP may indirectly induce compensatory proliferation through the recruitment of macrophages.
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fig1: Apoptotic stimuli activate caspases, triggering the proteolysis of a large number of intracellular substrates. The cleavage of many of these, including iCAD and lamins, is necessary for the morphological and biochemical changes of apoptosis. Other substrates have as yet undefined roles, while the cleavage of iPLA2 is critical for the paracrine signalling that induces compensatory proliferation. Cleavage of iPLA2 increases its activity, so raising the levels of PGE2 and LPC. PGE2 in turn activates EP2 G protein-coupled receptors on stem or progenitor cells. Intracellular signalling downstream of EP2 activates β-catenin and leads to cell proliferation. LPC and ATP may indirectly induce compensatory proliferation through the recruitment of macrophages.

Mentions: Studies in Drosophila, Xenopus, planaria, and Hydra have revealed a role for apoptotic cells in repair and regeneration [3–6], and the first clear evidence of its role in mammalian repair and regeneration came from a study using caspase- mice [7]. Skin and liver regeneration was investigated by studying the rate of wound healing in the skin and the rate of liver regeneration following partial hepatectomy. Li et al. reported that the loss of caspase-3 and/or caspase-7 markedly reduced the rate of tissue repair in both instances. Follow-up in vitro experiments showed that apoptotic cells released prostaglandin E2 (PGE2) in a caspase-dependent fashion and that this induced the proliferation of various stem cell types [7] (Figure 1).


"Dead Cells Talking": The Silent Form of Cell Death Is Not so Quiet.

Jäger R, Fearnhead HO - Biochem Res Int (2012)

Apoptotic stimuli activate caspases, triggering the proteolysis of a large number of intracellular substrates. The cleavage of many of these, including iCAD and lamins, is necessary for the morphological and biochemical changes of apoptosis. Other substrates have as yet undefined roles, while the cleavage of iPLA2 is critical for the paracrine signalling that induces compensatory proliferation. Cleavage of iPLA2 increases its activity, so raising the levels of PGE2 and LPC. PGE2 in turn activates EP2 G protein-coupled receptors on stem or progenitor cells. Intracellular signalling downstream of EP2 activates β-catenin and leads to cell proliferation. LPC and ATP may indirectly induce compensatory proliferation through the recruitment of macrophages.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3420226&req=5

fig1: Apoptotic stimuli activate caspases, triggering the proteolysis of a large number of intracellular substrates. The cleavage of many of these, including iCAD and lamins, is necessary for the morphological and biochemical changes of apoptosis. Other substrates have as yet undefined roles, while the cleavage of iPLA2 is critical for the paracrine signalling that induces compensatory proliferation. Cleavage of iPLA2 increases its activity, so raising the levels of PGE2 and LPC. PGE2 in turn activates EP2 G protein-coupled receptors on stem or progenitor cells. Intracellular signalling downstream of EP2 activates β-catenin and leads to cell proliferation. LPC and ATP may indirectly induce compensatory proliferation through the recruitment of macrophages.
Mentions: Studies in Drosophila, Xenopus, planaria, and Hydra have revealed a role for apoptotic cells in repair and regeneration [3–6], and the first clear evidence of its role in mammalian repair and regeneration came from a study using caspase- mice [7]. Skin and liver regeneration was investigated by studying the rate of wound healing in the skin and the rate of liver regeneration following partial hepatectomy. Li et al. reported that the loss of caspase-3 and/or caspase-7 markedly reduced the rate of tissue repair in both instances. Follow-up in vitro experiments showed that apoptotic cells released prostaglandin E2 (PGE2) in a caspase-dependent fashion and that this induced the proliferation of various stem cell types [7] (Figure 1).

Bottom Line: After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates.Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues.Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death.

View Article: PubMed Central - PubMed

Affiliation: Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, 53359 Rheinbach, Germany.

ABSTRACT
After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.

No MeSH data available.


Related in: MedlinePlus