WE ALL HAVE UNIQUE BRAINS

APOPTOSIS

APOPTOSIS

What is apoptosis?

Apoptosis is otherwise known as programmed cell death, or cell suicide. This happens every single day of your life: it happens in order to allow new cells in your body to replace the old cells. Depending on the location and the type of cell, the turnover of cells happens at different rates: skin and stomach cells die and are replaced the fastest.

What are the differences between apoptosis and necrosis?

Pic: http://www.nature.com/nrmicro/journal/v2/n10/images/nrmicro1007-f1.gif
Pic: http://www.nature.com/nrmicro/journal/v2/n10/images/nrmicro1007-f1.gif

Apoptosis is not the only method by which cells die:  as the picture alongside demonstrates, cells may become necrotic and die. I will also discuss this in the page called Necrosis. The main difference between apoptosis and necrosis is that necrotic cells do not leave behind apoptotic bodies which are capable of being digested, however cells which undergo apoptosis do. Another difference is that apoptosis does not trigger the inflammatory response, but necrosis does.

Under what circumstances does apoptosis happen?

Apoptosis can happen both under normal (physiological) and disease-related (pathological) circumstances. In normal circumstances, apoptosis happens when a cell no longer has a useful purpose. However, it can happen sooner if the cell is damaged beyond repair: the cells commit suicide in order to contain the damage within a localized area.

Physiological Reasons for Apoptosis

Pic: http://www.lpch.org/media/images/conditions/ei_0303.gif
Pic: http://www.lpch.org/media/images/conditions/ei_0303.gif
  • Maintenance of a constant number of cells: this happens a lot within the intestines and stomach lining
  • Differences in hormone levels: a classic example is the shedding of menstrual cells in women of child-bearing years because of the drop in hormones during the final week of the menstrual cycle.
  • Autoimmune disease prevention: by killing off of immune cells that attack ‘self’ before they mature
  • Is a defense mechanism against virus-infected cells and tumours

Pathological Reasons for Apoptosis

  • DNA damage: can be caused by extreme heat and cold, lack of oxygen, chemotherapy or radiation.
  • Cellular injury caused by (viral) infections: the induction of apoptosis can be done by either the virus or by our immune response.
  • Obstruction of organs due to blockage of ducts: often tends to occur within the pancreas, kidney and parotid glands.
  • Accumulation of misfolded proteins: this happens because of the transcription/translation process: the source of misfolded proteins therefore is the mutated DNA.

What are the mechanisms of apoptosis?

There are two different pathways with which apoptosis can happen: the mitochondrial (intrinsic) pathway or death receptor (extrinsic) pathway. Both of the pathways eventually come together and activate ‘executioner’ capases (proteins that cleave the amino acid cysteine). The final sequence of events is demonstrated below in the Smart Art graphic:

Smart Art Graphic: Original
Smart Art Graphic: Original

Intrinsic Pathway

Smart Art Graphic: Original
Smart Art Graphic: Original

The intrinsic pathway happens in cases of cellular injury triggered by withdrawl of growth factor, DNA damage or protein misfolding. The mitochondria are the organelles which produce the proteins that induce apoptosis. Once a certain level of damage is reached, sensors are triggered within the mitochondria. The Smart Art Graphic below demonstrates the intrinsic pathway. The process is regulated by Bcl-2 and Bcl-x (proteins which prevent apoptosis from happening if it is not necessary).

Extrinsic Pathway

Smart Art Graphic: Original
Smart Art Graphic: Original

The extrinsic pathway is triggered by interactions between ligands (ions attached to metallic atoms) and death receptors. Examples of such death receptors include Fas and TNF (tumour necrosis factor) receptors. The final two components of the intrinsic pathway interact with two components of the extrinsic pathway, as the Smart Art Graphic demonstrates alongside. Initiator capases can arise from cytochrome C.

What happens if apoptosis is stopped?

There is an infamous condition which you’ve probably heard of which happens as a result of apoptosis being stopped. The cells, in a sense, become immortal. You might have had it yourself, or you might know someone who has had this condition in their lives. Yes, I’m referring to cancer. I’ll be discussing this further in other pages, and I’ll refer to brain cancers in particular in Brain Pathology.