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Azerbaycan Saytlari

 »  Home  »  Endodontic Articles 16  »  Apoptosis: an introduction for the endodontist
Apoptosis: an introduction for the endodontist
Introduction.



P. G. Satchell, J. L. Gutmann & D. E.Witherspoon.
Private Practice Limited to Endodontics, Houston, USA.
Private Practice Limited to Endodontics, Dallas, USA.
Private Practice Limited to Endodontics, Plano, Texas, USA.


Introduction.
Apoptosis is essentially cell suicide, and was first described in the British Journal of Cancer in 1972 (Kerr et al. 1972). According to these authors, at the appropriate time and under certain conditions, cells self-destruct without damaging adjacent cells. This process is occurring constantly and can happen to seemingly healthy cells. Whilst it is unique to animals and is studied classically in the nematode worm Caenorhabditis elegans, it has been increasingly studied in vitro and in higher organisms.
There has been an explosion in the number of articles on the subject of apoptosis. A conservative estimate places the number at nearly 45 000.Whilst apoptosis has been a topic of extensive research in the scientific community for some time, it has received little attention in the endodontic literature. The purpose of this article is to familiarise the endodontist with apoptosis and to discuss some of the potential implications of apoptosis to endodontics.

Why and how is apoptosis important to endodontics?
Apoptosis plays a ubiquitous role in the body. Amongst other things, apoptosis is a key process in oral development (Vaahtokari et al. 1996, Harada et al. 1998, Cerri et al. 2000), the progression of oral disease (Polverini & Nor 1999), periradicular lesion development (Onishi et al.1997), resorption (Hughes & Boyce1997), immunological response and inflammation (Onishi et al. 1997), wound healing (Fanning et al.1999) and in certain pharmacological effects (Hughes et al.1995).The understanding of the ability of clinical materials to selectively induce or inhibit apoptosis is leading to new treatment modalities (Bamford et al. 2000). An understanding of the mechanisms of apoptosis may lead to adjunctive treatments for pulpal and periradicular diseases through yet unexplored pathways.

What is the apoptotic process?
The entire process of apoptosis takes about 1 h from initiation (Figs 1and 2).The initiating triggers are many and varied, and are grouped broadly as physiological or nonphysiological. These include, but are not limited to, the following: Fas ligands (Fas), tumour necrosis factor (TNF), nerve growth factor (NGF), nitric oxide (NO), lipopolysaccharide (LPS), host immune reactions, kinins and glucocorticoids (McKenna et al.1998).The best characterised apoptotic trigger is the Fas ligand, a member of the TNF super-family. The Fas receptor is a cell surface glycoprotein that mediates apoptotic signals from the cell surface into the cytoplasm (Yoshioka et al. 1996). When the Fas ligand binds to the Fas receptor on the cell membrane, the newly formed Fas complex is allowed to associate with intracellular proteins. The morphological changes of specific intracellular proteins induced by this complex result in the activation of other substances such as IL-1bconverting enzyme (ICE).
In this particular mechanism, and there are many, Procaspase (inactive form) is activated to the protease Caspase. An amplification cascade then ensues with Caspases activating other Caspases, eventually cleaving the host cell by acting on a variety of cell structures such as the nuclear membrane (Nicholson & Thornberry 1997). The cell shrinks in the process and there is a loss of cell-cell junctions resulting in detachment from adjacent cells. The chromatin condenses, the cytoplasm ‘blebs’ (forms so-called ‘pseudopods’) and the cell breaks up into fragments known as ‘apoptotic bodies’. Indirectly activated endonucleases lead to breakdown of the DNA (Kerr et al.1972) into multiples of180-200 base pair fragments (Cohen & Duke1984). Finally, either macrophages or adjacent cells phagocytose the apoptotic bodies (Kerr et al.1972) (Figs 1and 2).

Figure 1. The major stages of apoptosis include the initiating trigger (1) that leads to the activation of the intracellular mechanism for the apoptotic process (2). Morphological changes of the cell (3) include cell membrane changes that signal phagocytic cell recognition and elimination (4) without promoting inflammation.

The major stages of apoptosis include the initiating trigger

Figure 2. Various initiating triggers effect the activation of a central apoptotic signal. This central signal that can be blocked by bcl-2 leads to the activation of proteolytic enzymes via the caspase cascade. Those enzymes lead to morphological changes in the cell structures including the nucleus, cytoskeleton and membrane. Cell membrane changes include expression of proteins for recognition by phagocytic cells.

Various initiating triggers effect the activation of a central apoptotic signal