How Do Cells Know What to Do and When to Do It?
Article ID: 504153
Released: 7-Apr-2004 5:50 PM EDT
Source Newsroom: North Dakota IDeA Network of Biomedical Research Excellence (INBRE)
Newswise — The human body is made up of trillions of living cells that fulfill a myriad of purposes. But how do cells know what to do, when to do it and how to coordinate their actions?
Brij Singh, Ph.D., a biochemist at the University of North Dakota School of Medicine and Health Sciences, is developing a better understanding of calcium's role as a messenger in cell signaling and the channels that enable it to occur.
Advances in this area could help solve a variety of human health problems, ranging from neurodegenerative diseases to cancer to Sjogren syndrome, a disease caused when the immune system attacks the glands that make saliva and tears. It could also serve as a useful diagnostic tool in detecting and treating cancer.
"Calcium signaling is used from cell division to cell death," Singh says. "Most of those processes " from when a cell divides until it dies " are controlled by calcium."
The simple act of picking up a pen requires muscle cells to contract in a manner that makes the arm move toward the pen and the fingers grasp it. Calcium stored within muscle cells is released, sending the signals that tell the cells to contract.
While calcium's role in cell signaling is well known, what's not well understood is how calcium channels are controlled. Singh's research has identified transient receptor potential (TRP) proteins as ion channels which transfer calcium into cells.
Muscles cells and nerve cells, which function by generating electrical pulses, are excitable. They have a multitude of calcium channels besides TRP proteins. All other cells are nonexcitable, and TRP proteins are the major calcium channels in these cell types.
"What we are doing is fairly new," he says. "The calcium channel activity of TRP proteins was identified only a few years ago. We are studying how the TRP calcium channels function and attempting to discover the mechanisms to turn them on and off whenever needed.
"These channels are very tightly regulated. If there's no calcium in the cell, the cell will die. If there's too much calcium in the cell, it will die," Singh says."If there's a problem with these channels, we need to understand the causes for it happening."
A native of India, Singh is an assistant professor in the Department of Biochemistry and Molecular Biology at the UND medical school. He received a Ph.D. in molecular biochemistry from Bhopal University in India. Before joining UND early in 2003, he was a researcher with the NIH National Institute of Dental and Craniofacial Research.
For the past five years, his work has focused on salivary glands because of their importance in maintaining oral health. It is estimated that as many as 4 million people in the United States suffer from low saliva production caused by Sjogren syndrome. In addition, patients who receive radiation therapy for cancers in the head and neck lose their ability to produce saliva.
With a better understanding of calcium signaling in nonexcitable cells, ingh's research demonstrates that it is possible to stimulate saliva glands by using gene therapy.
"We have shown that when we inject TRP protein into rats, we can increase saliva production," he says.
Singh's research has also identified other TRP protein channels that enable calcium to enter a cell. However, they each work in different manners. Some channels not only transport calcium, but also regulate cell processes, such as those that cause cancer and neurodegenerative diseases such as Parkinson and Alzheimer.
Some TRP proteins are found only in cancerous cells, which make them a useful biomarker for the early discovery and treatment of cancer.
"If these proteins are there, we can say the cancer will develop in a certain amount of time," Singh says. "If we don't see those proteins, we can say that there is no cancer."
With Parkinson disease, Singh's research indicates that a certain TRP protein stops neurons from dying. Through gene therapy, he believes it might be possible to stimulate the production of the protein to protect brain cells. The same treatment might also be effective for Alzheimer disease, which functions in a similar manner.
Singh is also engaged in research collaborations at the UND medical school with Manuchair Ebadi, Ph.D., director of the Center of Excellence in Neurosciences; Donald Sens, Ph.D., professor in the Department of Surgery; and Gene Homandberg, Ph.D., chair of the Department of Biochemistry and Molecular Biology.
Ebadi specializes in neurodegenerative diseases such as Parkinson, Alzheimer and multiple sclerosis. Sens is studying biomarkers related to breast and bladder cancer. Homandberg is recognized for his studies on cartilage degeneration in osteoarthritis.
High-resolution digital images to accompany this news release are available here:http://www.med.und.nodak.edu/brin/Images.htm
Recently published research articles:
Brazer, S.W., Singh B.B., Liu, X., Swaim, W & Ambudkar I.S (2003) caveolin-1 contributes to assembly of store-operated Ca2+ influx channels in regulating plasma membrane localization of TRPC1. Journal of Biological Chemistry. 278. 27208-15.
Singh, B.B., Liu, X & Ambudkar, I.S. (2003) Acidic amino acid residues in the S5-S6 region of TRPC1 contributes to store-operated Ca2+ influx. Journal of Biological Chemistry. 278. 11337-11343.