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February 2005
Zinc and Apoptosis (programmed cell death) 
 


Zinc is an essential trace metal-it is necessary for life. In the absence of zinc cellular growth cannot occur at a normal rate and eventually all animals die from this lack —this is called zinc deficiency. However, if too much zinc is present cells also cannot function normally and eventually all animals will die from this excess - this is called zinc toxicity. Thus, there is a balance in nature between too little and too much zinc in order to obtain optimal growth and development.

On a cellular level zinc plays a critical role in cell synthesis. About 1/3 of all proteins have zinc structures in their internal machinery —these structures are called zinc fingers. Zinc is also a critical component in many enzyme systems and without enough zinc these enzymes cannot perform their normal function–this is part of the reason why animals die if they do not have enough zinc in their body. If animals are exposed to too much zinc these cellular mechanisms also do not function normally and animals become ill. Fish are particularly sensitive to zinc and will die if they are exposed to too much zinc in water.

One of the critical functions of all animals is to eat —to maintain adequate nutrition. Two of the mechanisms by which eating is controlled occurs in the ability to taste and to smell. One of the enzymes which is critical to maintain taste and smell function is a zinc dependent metalloenzyme called carbonic anhydrase (CA) VI. If zinc is not present in the body in adequate amounts and zinc deficiency occurs this enzyme does not function correctly and/or is not made in adequate amounts; the animal loses its ability to taste and smell. This mechanism which controls food intake causes animal death since animals no longer want to eat; they suffer from malnutrition and eventually die.

CA VI functions in the taste and smell systems as a growth factor which stimulates stem cells to induce maturation of the cells which maintain taste and smell function. But it also plays a role in programmed cell death or APOPTOSIS (see Jan 2005 What’s New). If there is too little zinc, apoptosis increases and cells die abnormally. If there is too much zinc, apoptosis also becomes altered and cells may die for several metabolic reasons. Thus, zinc, along with a host of other substances, is part of the control process by which apoptosis occurs.

We also know that zinc is a physiological mitogen-it causes cells of the immune system to grow and mature, particularly in response to introduction of any microbe, including a virus, that might attack us. Zinc also increases our resistance to any incoming microbe or virus by inactivating viruses. For these reasons, zinc has been used as a therapy for inhibiting viral growth. It has been used in several proprietary preparations to inhibit cold symptoms. Most of these zinc treatments have been used orally since it is best absorbed and metabolized in the gastrointestinal tract and distributed to all tissues in a physiological manner.

Some zinc preparations used to treat colds have also been used as a nasal spray. The blood vessels in the nose are very amenable to absorbing any substance entering the nose and they metabolize such substances well and rapidly. Thus, zinc can easily be absorbed into the body upon entry through the blood vessels in the nose, perhaps too easily, since the cells which control zinc absorption in the gastrointestinal tract are not present in the blood vessels in the nose. However, cells of the olfactory epithelium are also present in the nose and their growth and development, the function of their stem cells, their cellular growth and cellular development, is critically dependent upon

  1. function of the zinc dependent enzyme CA VI,
  2. action of zinc in controlling cell growth and cell death and
  3. the local absorption of zinc by the nasal blood vessels.

Since some cells of the olfactory epithelium live and die on a daily basis zinc is critical to maintain normal cellular activity and thereby, normal smell function. However, if any excess zinc were introduced directly into the nose this zinc could disturb the balance between cell growth and cell death, shifting the balance toward excess cell death or increased apoptosis and thereby cause loss of smell. Local effects of excess zinc could also produce a direct toxic effect as in fish. Introduction of too much zinc into the nose is one mechanism whereby a product now on the market as a zinc containing nasal spray may cause loss of smell among people who use this drug to ward off symptoms of a viral cold.

For further information about the use of zinc as an antiviral or anticold agent see:

  1. Covington, TR, Henkin, R, Miller, S, Sassetti, M, Wright, W. Treating the Common Cold. Ill. J. Nurse Pract. 8:77-88, Chicago, IL 2004.

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