Protein bodyguards

THE human body has an impressive battery of security guards. Everybody knows about the infection-fighting capabilities of white blood corpuscles. But there are other little known body defenders, such as the heat-shock proteins, that are equally valiant and useful.

The heat-shock proteins (HSP) are produced by cells in response to a sudare more than mere defenders. Says Elizabeth C Craig, a biochemist at the University of Wisconsin, who was recently in Delhi to attend an international conference on molecular biology and biochemistry, "Throughout the life of a cell, many of these proteins take part in crucial events, such as chaperoning errant proteins from going astray from their ordained paths as well as nursing injured proteins back to well being." Scientists have Heat smart proteins under the microscope den increase in temperature of the surroundings, or when the cells are exposed to heavy metals, alcohols, and various other toxic materials. Because all the causes that induce production of heatshock proteins are expressions of stress, these proteins are also referred to as stress proteins.

The proteins, which are found in bacteria, viruses, plant and animal cells, are more than mere defenders. Says C Craig a biochemist at the University of Wisconsin, who was recently in Delhi to attend an international conference on molecular biology and biochemistry, "Through a life the cell , many of these proteins take part in crucial events, such as chaperoning errant proteins from going astray from their ordained path as well as nursing injured proteins back to well being."

Scientists have found that the stress proteins act as bodyguards or janitors for various VIP molecules such as the ATP molecule, the body's energy producer. They have been found crucial for the survival of certain viruses that depend on the cellular feast provided by their hosts. In the absence of genes that code for these proteins, many viral protein molecules fail to assemble or fold properly.

Stress proteins also serve a pivotal role in the regulation of other systems of proteins and cellular responses. For instance, says Craig, "HSP 90 has been known to act as a leash on certain viral enzymes that are believed to damage proteins that regulate cellular growth' Similarly, HSP 90 is thought to play a crucial role in keeping out of business certain steroid receptors of hormones that trigger cell differentiation -inducing cells to develop different to take on their destined roles whether it be as a brain cell or a muscle cell, instance.
Stress response Scientists are now beginning to realise the practical applications of the streft response. Clinicians, for example, are examining changes in stress protein Irvels as markers for tissue and organ injury. Cells that produce high levels of stress proteins appear better able to Survive heart attack than cells that do not Such a therapeutic approach mioreduce the tissue damage from hean attack incurred during surgery, say Craig.

An exciting application of strew proteins concerns their role a immunology and infectious diseasm. such as malaria, tuberculosis,and leprosy, that affect millions of people ew"year. Says Y D Sharma, a researcher a the Delhi-based All India Institute of -Medical Sciences who has worked an the possibility of making a malaria rxcine out Of HSP found in the mal" parasite, "Immunologists have found that stress proteins made by thtm organisms are often the major anther protein targets that the immune sw tem uses to re@ognise and destroy the invaders. The human immune system may be constantly on the lookout 11pr alien forms of stress proteins."Light to light. manufacturing a fibre preform In some of the autoimmune diseases, such as rheumatoid arthritis and spondylitis, antibodies against patient's own stress proteins are sometimes observed. If these observations are confirmed on a large number of patients, they may prove helpful in the diagnosis and perhaps treatment of autoimmune disorders, believes Sharma.

Stress proteins, scientists believe, could also prove useful in diagnosing diseases caused by the bacterium Chlamydia trachomatis, which is responsible for trachoma, probably the world's leading cause of preventable blindness, and pelvic inflammatory disease, a major cause of infertility in women. Infection with Chlamydia generally triggers the production of antibodies against chlarnydial antigens, some of which are stress proteins. So measurements of antibodies against chlamydial stress proteins may prove useful for identifying women at great risk from infertility or ectopic pregnancies -development of the foetus elsewhere than in the uterus.

The ability to manipulate stress response may also prove important in developing new approaches to treating cancer. Tumours often appear to be more ther-mally sensitive than normal tissue. Elevating the temperature of tissues to eradicate turnouts is one idea that -is-4till at the experimental stages. There is a catch here, however, Because stress proteins afford cells added protection, anticancer therapies that induce a stress response may make a tumour resistant to subsequent treatments.

Scientists are also now beginning to explore the potential use of the stress response in toxicology. Changes in the levels of the stress proteins, particularly those produced only in injured cells, may prove useful for assessing the toxicity of drugs, cosmetics, food additives and other products.

A Employing recombinant-DNA technology, scientists have created "stress reporter" genes that might be used to screen for biological hazards. In such cells, the DNA sequences that control the activity of the stress protein genes are linked to a reporter gene that encodes Cells that produce high levels of stress proteins are better eqLdpped to survive heart attacks an enzyme. When these cells experience some metabolic stress, and produce more stress proteins, they also make the reporter gene which can be easily detected.

Using such reporter cells, investigators can easily determine the extent of the stress response induced by chemical agents or treatments. "If such assays prove reliable says Rekha Chaturvedi of the Centre for Biochemicals in Delhi, they could ultimately reduce or even replace the use of animals in toxicology testing."

A slightly modified technique could also be used to monitor the dangers of environmental pollutants, many of which evoke stress responses. Towards that end, scientists have begun developing transgenic stress reporter organisms. For example, scientists have created transgenic worms, which when exposed to various pollutants, express the reporter enzyme and turn blue. Currently, scientists are trying to find out whether such reporter genes can be used for monitoring other pollutants.

Medical Research Science & Technology