DEAN SENSUI / DSENSUI@STARBULLETIN.COM
Dr. Andrea Fleig and Dr. Reinhold Penner take a look at images and computer data to track and measure the presence of magnesium in cellular structures. They recently published a paper that identifies the mechanism that moves magnesium through the cell.
Researchers at
Queen’s solve major
biochemical mysteryTheir findings on how cells use
magnesium may help treat cancerMagnesium performs various functions
A discovery by two biomedical researchers at the Queen's Medical Center and others opens possibilities for new drugs and compounds targeting cancer cells and other diseases.
Drs. Andrea Fleig and Reinhold Penner and collaborators in Washington and Japan identified how magnesium, a crucial element for human health, gets into cells.
Magnesium was "sort of a forgotten ion" because no one knew how it was regulated, Penner said. "They knew it was important, but how the hell does it go into the cells or how does it get out of cells?"
Transfer mechanisms were found for magnesium in yeast and other organisms, but the proteins couldn't be found in mammals, Fleig said: "So there must be a different mechanism for magnesium."
"We just happened to find that gene," Penner said. "We finally know how magnesium is transported into cells and how it affects cell growth and proliferation."
The mechanism is a novel ion channel, a protein that forms tiny pores like gates in cellular membranes for passage of ions such as magnesium, calcium, potassium and sodium.
"It is the first magnesium selective channel ever to be found," Fleig said.
The gene is called TRPM7 and the ion channel is known as MagNuM, meaning magnesium-nucleotide-regulated metal-currents.
The findings, which Penner and Fleig discussed in an interview, are reported in the cover story of the July 25 issue of Cell magazine. The primary author is Dr. Arnold Scharenberg of the University of Washington and Children's Hospital and Regional Medical Center, Seattle. Other researchers were Megan K. Smith, Catherine O. Johnson, Anne-Laure Perraud and Carsten Schmitz, all on Scharenberg's team, and Tomohiro Kurosaki and Kazunori Inabe at Kansai Medical University in Japan.
They demonstrate in the article that TRPM7 "is absolutely critical for cell survival, cell growth and cell proliferation," Fleig said.
Certain cells grow uncontrollably in cancer, she said, so if the pathway is knocked out and magnesium is inhibited in those cells, "we can stop their growth and possibly even kill the existing tumor cells."
Fleig and Penner, affiliated with the University of Hawaii John A. Burns Medical School, are world-renowned molecular researchers who have made a series of discoveries.
They are studying eight ion channels, seven of the same family and one that's different. "All are involved in calcium signaling or magnesium signaling," Fleig said.
Intellectual property developed in their Laboratory of Cell and Molecular Signaling at Queen's has been licensed to a company in Boston and they are in discussions with pharmaceuticals for drug development involving another ion channel, they said.
They are also working with big companies to develop drugs based on their findings of the magnesium-conducting ion channel.
"Most people know magnesium is really important for fireworks, but few people realize magnesium is equally important as calcium," said Penner.
A Web site is devoted just to magnesium and drinking water and health with numerous links to conditions the element may help to prevent or treat, he noted.
People in areas with hard water overall have fewer heart attacks than those with soft water because softening water deionizes it, Fleig pointed out. "It (water softening) takes out all the minerals that are important for human life.
"Magnesium is a key protein to cellular survival. It's in every single tissue of the body," she said.
A lot of people don't know they're deficient in magnesium, which can affect virtually all of a person's organ systems, Penner said.
Many diseases involve multiple factors and people don't know which is most important, he said. If ion channels open too much or too little, they may contribute to a number of diseases, he said.
"Now that we know what this protein or ion channel is doing, we can see whether some diseases people are suffering from are actually related to this mechanism," he said. "Now we can actually go into animal models and see what happens when the function of this protein, for example, is compromised and what happens when we stimulate the open state of this ion channel.
"If the protein is knocked out of the cell, which can be done genetically, the cell dies," Penner said. "It's absolutely required for cell survival. It's the only ion channel known that is vital ... If it is not working or working too much, your cells will die.
"Magnesium has been an orphan ion," Fleig said, noting that its role in osteoporosis was eye-opening for her. It's as important as calcium to prevent the long-term disease because 65 percent of magnesium is stored in the bones and teeth, she said.
Also, she said, magnesium and calcium "are counter players." If there is too much of one, the other will be affected, she said.
A two-to-one ratio of calcium to magnesium must be maintained for balance with supplements, she said. "If you don't take magnesium and you take loads of calcium, you can still have a calcium deficiency."
Penner and Fleig are funded by the National Institutes of Health, the Queen Emma Research Foundation, the Victoria S. and Bradley L. Geist Foundation and the Leahi Foundation.
BACK TO TOP |
Magnesium performs
various functions
Magnesium is required for hundreds of biochemical functions in the body, helping to keep heart rhythm steady and bones strong and contribute to energy and cardiovascular activity.
It acts as a tranquilizer to relax muscles and the gastrointestinal tract and is called an "anti-stress" mineral.
It is increasingly used to prevent or treat certain health conditions. For example, it has been used to lower blood pressure, influence activity of insulin to control blood glucose levels in diabetes, reduce risk of coronary artery spasms and treat premenstrual syndrome.
A magnesium deficiency can cause metabolic changes that may contribute to stroke and heart attacks. Migraines, attention deficit disorder, fibromyalgia, asthma and allergies are among other conditions that have been linked to a lack of the nutrient.
Symptoms of too little magnesium include sensitivity to noise and bright lights, irritability, mental depression, twitching, trembling, apprehension, insomnia, muscle weakness, difficulty breathing and swallowing, anxiety, heart arrhythmia, angina, high blood pressure and cramps and urinary spasms, among others.
Too much magnesium from high doses of supplements may cause diarrhea and toxicity associated with kidney failure.
Many foods supply magnesium, usually in small amounts. Green vegetables such as spinach are good sources because the chlorophyll molecule contains magnesium. Other good sources are nuts, seeds and whole grains.
The recommended daily allowance of magnesium, which some authorities say should be doubled, is about 350 milligrams for men and 300 milligrams for women, increasing to about 450 milligrams during pregnancy and lactation.
Sources: "Facts About Dietary Supplements," National Institutes of Health, and "Staying Healthy with Nutrition, the Complete Guide to Diet and Nutritional Medicine," by Dr. Elson M. Haas.
