Apoptosis

Background

As with all living beings, cells in multicellular organisms are programmed to die.  This process of programmed cell death (PCD) is referred to as apoptosis (1).  Like other cellular processes, apoptosis involves a defined sequence of events, the culmination of which results in cell death.  Being a natural process, apoptosis does not trigger a pain response.  Research shows that, on average, adult humans go through daily apoptosis of approximately 50-70 billion cells (1).

Apoptosis is just as essential as other vital cellular processes and its significance can be gauged from the fact that tumors develop when apoptosis fails and cells continue to multiply.  This lack of apoptotic control is harmful because it causes cancer, degenerative diseases such as diabetes mellitus and multiple sclerosis (2).  Apoptosis is also the process through which the body gets rid of otherwise detrimental extraneous components from the body.  On the other hand, autoimmune diseases may occur due to excessive apoptosis (2).

Although apoptosis was discovered approximately a century ago (1), scientists started showing an interest in this process in the early 1970s (2).  However, it was only recently that scientists identified apoptosis inducing molecules and the related genes that control the process.  The identification and discovery of related genes clearly demonstrates the role apoptosis plays in controlling occurrence and prevention of diseases.

Apoptosis is a critical process during organism development.  For instance, adequate cell death is responsible for clearly defined fingers in human beings.  During embryonic development the palm and toe have humble beginnings starting from small bud-like structures.  Active differentiation and controlled apoptosis is able to regulate the formation of individually free digits.  Failure of normal PCD occurrence results in individuals born with some or all fingers fused together.  Other well-known instances of apoptosis are the absorption of a tadpole tail as it grows into an adult frog, the removal of virus infected cells and the monthly sloughing off of the uterine lining at the time of menstruation (3).

Clinical Utility

Apoptosis helps maintain a constant number of cells in living organisms, a condition referred to as homeostasis.  This is achieved by balancing the creation of new cells with a necessary number of regularly dying cells (1).  The impact of dysregulation of apoptosis is an emerging field of study as researchers attempt to comprehend the effects of extreme apoptosis, in cases where it is too little or really extensive.

There are a number of pathways that can cause dysregulation of apoptosis and affect many biological processes.  A malfunction in any of these pathways can cause the cell to live past its intended lifespan, causing the newly formed malfunction to be passed on to a future generation of cells.  This increase in faulty cells may lead to cancer causing cells or a number of other diseases.  Mechanisms such as apoptosis have been implicated in inflammatory conditions, cancers, immune diseases and viral infections.  One example is a type of lung cancer that has been found such that an inhibitor of an apoptosis protein is overexpressed, decreasing pro-apoptosis molecules and causing increased replication of damaged cells despite their identification as being malfunctioning by the immune system.

The p53 protein is considered to be a primary precursor of the apoptosis process and p53 has been observed to induce cell death in the event the cell fails to function and/or develop normally.  As expected, cancer patients show high levels of mutated p53 gene, thus, producing a defective protein with little or no apoptotic effect.  As a result, deficiency of the p53 protein prevents cell death and cells continue to multiply, giving rise to tumors (3).

Cells will show regular growth when favorable indicators are available, such as sufficient nutrients and interleukin-2 (IL-2).  The lack of growth supporting factors or the occurrence of growth restricting conditions triggers the apoptosis process.  Cell death can occur due to intrinsic factors, such as abnormally high calcium levels, damaged DNA, x-rays and unusually low concentration of nutrients.  External factors such as toxins, injury, cytokines and a hormonal imbalance can initiate apoptosis.

 

References:
1.    Apoptosis – Wikipedia, the free encyclopedia, http://en.wikipedia.org/wiki/Apoptosis
2.    Advances in apoptosis research – PNAS, http://www.pnas.org/content/94/24/12736.full
3.    Apoptosis, http://www.biology-pages.info/A/Apoptosis.html

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